Publications by authors named "Xijing Zhang"

34 Publications

[Recent progress of antimicrobial peptides in sepsis treatment].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2021 May;33(5):626-629

Department of Critical Care Medicine, the First Affiliated Hospital of Air Force Military Medical University, Xi'an 710000, Shaanxi, China. Corresponding author: Zhang Xijing, Email:

Sepsis is a life-threatening organ dysfunction due to the dysregulation of host responses during infection. Severe systemic inflammatory response syndrome (SIRS) is the primary pathophysiological feature. Despite the classical antibiotic therapies play an important role in sepsis, the emergence of multi-resistant bacteria makes a greater challenge in clinical. Antimicrobial peptides (AMP) which consist of small cationic peptides, can be found in most organisms. As a result of their board-spectrum antibacterial activities and immunoregulatory functions, AMPs may have an excellent effect on the treatment of sepsis. In this review, we will discuss the basic role of AMPs in sepsis treatment and their application prospect and the challenges which need to be resolved in order to provide ideas for clinical application of AMPs.
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http://dx.doi.org/10.3760/cma.j.cn121430-20200828-00602DOI Listing
May 2021

An MD2-perturbing peptide has therapeutic effects in rodent and rhesus monkey models of stroke.

Sci Transl Med 2021 06;13(597)

Translational Research Institute of Brain and Brain-Like Intelligence and Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, Tongji University School of Medicine, Shanghai 200434, China.

Studies have failed to translate more than 1000 experimental treatments from bench to bedside, leaving stroke as the second leading cause of death in the world. Thrombolysis within 4.5 hours is the recommended therapy for stroke and cannot be performed until neuroimaging is used to distinguish ischemic stroke from hemorrhagic stroke. Therefore, finding a common and critical therapeutic target for both ischemic and hemorrhagic stroke is appealing. Here, we report that the expression of myeloid differentiation protein 2 (MD2), which is traditionally regarded to be expressed only in microglia in the normal brain, was markedly increased in cortical neurons after stroke. We synthesized a small peptide, Trans-trans-activating (Tat)-cold-inducible RNA binding protein (Tat-CIRP), which perturbed the function of MD2 and strongly protected neurons against excitotoxic injury in vitro. In addition, systemic administration of Tat-CIRP or genetic deletion of MD2 induced robust neuroprotection against ischemic and hemorrhagic stroke in mice. Tat-CIRP reduced the brain infarct volume and preserved neurological function in rhesus monkeys 30 days after ischemic stroke. Tat-CIRP efficiently crossed the blood-brain barrier and showed a wide therapeutic index for stroke because no toxicity was detected when high doses were administered to the mice. Furthermore, we demonstrated that MD2 elicited neuronal apoptosis and necroptosis via a TLR4-independent, Sam68-related cascade. In summary, Tat-CIRP provides robust neuroprotection against stroke in rodents and gyrencephalic nonhuman primates. Further efforts should be made to translate these findings to treat both ischemic and hemorrhagic stroke in patients.
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http://dx.doi.org/10.1126/scitranslmed.abb6716DOI Listing
June 2021

Rosmarinic acid protects rats against post-stroke depression after transient focal cerebral ischemic injury through enhancing antioxidant response.

Brain Res 2021 04 4;1757:147336. Epub 2021 Feb 4.

Department of Anesthesiology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi 710032, China. Electronic address:

Rosmarinic acid (RA), a natural polyphenol, possesses potent antioxidant and anti-inflammatory activities. To evaluate the ability of RA to cure ischemic stroke and post-stroke depression (PSD), rats were treated with various doses of RA after cerebral ischemia. Neurological deficits and infarct volume of the brain were measured. The activities of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) were examined at different time points. In addition, a forced swimming test and sucrose preference test were performed to detect the anti-depressive effects of RA. Our results revealed RA administration significantly alleviated neurological deficits and reduced infarct volumes. RA attenuated the decrease of SOD, CAT activities and GSH levels in the ischemic penumbra of the brain. Most importantly, RA treatment alleviated the depression behaviors. Increased expression of Nrf2 was also induced by RA, while down regulation Nrf2 by Nrf2-short-hairpin RNA sequences reversed the increasing activity of SOD and CAT induced by RA, as well as the protection against PSD. The present study indicates that RA exerts a potent neuroprotective effect against stroke and PSD, which could be a promising therapeutic intervention for stroke.
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http://dx.doi.org/10.1016/j.brainres.2021.147336DOI Listing
April 2021

Extracorporeal Membrane Oxygenation for SARS-CoV-2 Acute Respiratory Distress Syndrome: A Retrospective Study From Hubei, China.

Front Med (Lausanne) 2020 12;7:611460. Epub 2021 Jan 12.

Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The data on long-term outcomes of patients infected by SARS-CoV-2 and treated with extracorporeal membrane oxygenation (ECMO) in China are merely available. A retrospective study included 73 patients infected by SARS-CoV-2 and treated with ECMO in 21 intensive care units in Hubei, China. Data on demographic information, clinical features, laboratory tests, ECMO durations, complications, and living status were collected. The 73 ECMO-treated patients had a median age of 62 (range 33-78) years and 42 (63.6%) were males. Before ECMO initiation, patients had severe respiratory failure on mechanical ventilation with a median PO/FiO of 71.9 [interquartile range (IQR), 58.6-87.0] mmHg and a median PCO of 62 [IQR, 43-84] mmHg on arterial blood analyses. The median duration from symptom onset to invasive mechanical ventilation, and to ECMO initiation was19 [IQR, 15-25] days, and 23 [IQR, 19-31] days. Before and after ECMO initiation, the proportions of patients receiving prone position ventilation were 58.9 and 69.9%, respectively. The median duration of ECMO support was 18.5 [IQR 12-30] days. During the treatments with ECMO, major hemorrhages occurred in 31 (42.5%) patients, and oxygenators were replaced in 21 (28.8%) patients. Since ECMO initiation, the 30-day mortality and 60-day mortality were 63.0 and 80.8%, respectively. In Hubei, China, the ECMO-treated patients infected by SARS-CoV-2 were of a broad age range and with severe hypoxemia. The durations of ECMO support, accompanied with increased complications, were relatively long. The long-term mortality in these patients was considerably high.
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http://dx.doi.org/10.3389/fmed.2020.611460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835137PMC
January 2021

Tracheostomy in 80 COVID-19 Patients: A Multicenter, Retrospective, Observational Study.

Front Med (Lausanne) 2020 17;7:615845. Epub 2020 Dec 17.

Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.

The outbreak of coronavirus disease 2019 (COVID-19) has led to a large and increasing number of patients requiring prolonged mechanical ventilation and tracheostomy. The indication and optimal timing of tracheostomy in COVID-19 patients are still unclear, and the outcomes about tracheostomy have not been extensively reported. We aimed to describe the clinical characteristics and outcomes of patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia who underwent elective tracheostomies. The multi-center, retrospective, observational study investigated all the COVID-19 patients who underwent elective tracheostomies in intensive care units (ICUs) of 23 hospitals in Hubei province, China, from January 8, 2020 to March 25, 2020. Demographic information, clinical characteristics, treatment, details of the tracheostomy procedure, successful weaning after tracheostomy, and living status were collected and analyzed. Data were compared between early tracheostomy patients (tracheostomy performed within 14 days of intubation) and late tracheostomy patients (tracheostomy performed after 14 days). A total of 80 patients were included. The median duration from endotracheal intubation to tracheostomy was 17.5 [IQR 11.3-27.0] days. Most tracheotomies were performed by ICU physician [62 (77.5%)], and using percutaneous techniques [63 (78.8%)] at the ICU bedside [76 (95.0%)]. The most common complication was tracheostoma bleeding [14 (17.5%)], and major bleeding occurred in 4 (5.0%) patients. At 60 days after intubation, 31 (38.8%) patients experienced successful weaning from ventilator, 17 (21.2%) patients discharged from ICU, and 43 (53.8%) patients had died. Higher 60 day mortality [22 (73.3%) vs. 21 (42.0%)] were identified in patients who underwent early tracheostomy. In patients with SARS-CoV-2 pneumonia, tracheostomies were feasible to conduct by ICU physician at bedside with few major complications. Compared with tracheostomies conducted after 14 days of intubation, tracheostomies within 14 days were associated with an increased mortality rate.
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http://dx.doi.org/10.3389/fmed.2020.615845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793766PMC
December 2020

Microglia: A Potential Therapeutic Target for Sepsis-Associated Encephalopathy and Sepsis-Associated Chronic Pain.

Front Pharmacol 2020 27;11:600421. Epub 2020 Nov 27.

Department of Anaesthesiology and Perioperative Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.

Neurological dysfunction, one of the severe manifestations of sepsis in patients, is closely related to increased mortality and long-term complications in intensive care units, including sepsis-associated encephalopathy (SAE) and chronic pain. The underlying mechanisms of these sepsis-induced neurological dysfunctions are elusive. However, it has been well established that microglia, the dominant resident immune cell in the central nervous system, play essential roles in the initiation and development of SAE and chronic pain. Microglia can be activated by inflammatory mediators, adjacent cells and neurotransmitters in the acute phase of sepsis and then induce neuronal dysfunction in the brain. With the spotlight focused on the relationship between microglia and sepsis, a deeper understanding of microglia in SAE and chronic pain can be achieved. More importantly, clarifying the mechanisms of sepsis-associated signaling pathways in microglia would shed new light on treatment strategies for SAE and chronic pain.
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http://dx.doi.org/10.3389/fphar.2020.600421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729164PMC
November 2020

Association of hypertension and antihypertensive treatment with COVID-19 mortality: a retrospective observational study.

Eur Heart J 2020 06;41(22):2058-2066

Department of Cardiology, Xijing Hospital, Changle West Road, Xi'an, 710032, China.

Aims: It remains unknown whether the treatment of hypertension influences the mortality of patients diagnosed with coronavirus disease 2019 (COVID-19).

Methods And Results: This is a retrospective observational study of all patients admitted with COVID-19 to Huo Shen Shan Hospital. The hospital was dedicated solely to the treatment of COVID-19 in Wuhan, China. Hypertension and the treatments were stratified according to the medical history or medications administrated prior to the infection. Among 2877 hospitalized patients, 29.5% (850/2877) had a history of hypertension. After adjustment for confounders, patients with hypertension had a two-fold increase in the relative risk of mortality as compared with patients without hypertension [4.0% vs. 1.1%, adjusted hazard ratio (HR) 2.12, 95% confidence interval (CI) 1.17-3.82, P = 0.013]. Patients with a history of hypertension but without antihypertensive treatment (n = 140) were associated with a significantly higher risk of mortality compared with those with antihypertensive treatments (n = 730) (7.9% vs. 3.2%, adjusted HR 2.17, 95% CI 1.03-4.57, P = 0.041). The mortality rates were similar between the renin-angiotensin-aldosterone system (RAAS) inhibitor (4/183) and non-RAAS inhibitor (19/527) cohorts (2.2% vs. 3.6%, adjusted HR 0.85, 95% CI 0.28-2.58, P = 0.774). However, in a study-level meta-analysis of four studies, the result showed that patients with RAAS inhibitor use tend to have a lower risk of mortality (relative risk 0.65, 95% CI 0.45-0.94, P = 0.20).

Conclusion: While hypertension and the discontinuation of antihypertensive treatment are suspected to be related to increased risk of mortality, in this retrospective observational analysis, we did not detect any harm of RAAS inhibitors in patients infected with COVID-19. However, the results should be considered as exploratory and interpreted cautiously.
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http://dx.doi.org/10.1093/eurheartj/ehaa433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314067PMC
June 2020

[How to improve the teaching ability of young teachers of critical care medicine?]

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2020 Mar;32(3):371-373

Department of Intensive Care Unit, Xijing Hospital, Air Force Medical University, Xi'an 710032, Shaanxi, China.

Intensive care unit (ICU) in teaching hospital plays important roles in teaching work. The young teachers of critical care medicine are gradually becoming the backbone of teaching work. Improving the teaching ability of young teachers is essential to increase learning motivation of the students and to promote the overall teaching quality of critical care medicine. Therefore, pay attention to help the young teachers of critical care medicine to improve their teaching skill is good for enhancing the faculty developing of critical care medicine, as well as essential for the prosperity and sustainable development of critical care medicine. Based on the problems existing during the teaching process of young teachers of critical care medicine and aimed to train excellent teachers, this article discussed the teaching methods and experience of young teachers of critical care medicine which focuses on teaching program design, class affinity improvement and humanistic education in order to improve the teaching level of young teachers of critical care medicine.
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http://dx.doi.org/10.3760/cma.j.cn121430-20200102-00087DOI Listing
March 2020

Exploring the Effects of Patient Activation in Online Health Communities on Patient Compliance.

Telemed J E Health 2020 11 4;26(11):1373-1382. Epub 2020 Feb 4.

Department of Information Management, School of Economics and Management, Beijing Jiaotong University, Beijing, China.

Online health communities (OHCs) are one of the developments related to online health. Patient compliance plays a vital role in improving health treatment outcomes. Patient activation is associated with patient activities in OHCs, such as physician-patient communication and health information seeking. In other words, OHCs influence patient compliance. Therefore, identifying the relationship between patient activation in OHCs and patient compliance is important for improved health outcomes. This study established a research model consisting of one independent variable (patient activation), four mediators (physician-patient communication, health information seeking, perceived information asymmetry, and e-health literacy), one dependent variable (patient compliance) and four control variables (gender, age, education level, and status). Data were obtained through a web-based survey, involving a total of 387 valid participants in China. These data were analyzed and tested through structural equation modeling and partial least squares. Patient activation positively affects patient compliance through the mediation of physician-patient communication, health information seeking, perceived information asymmetry, and e-health literacy. Perceived information asymmetry has no direct effect on patient compliance. However, perceived information asymmetry affects patient compliance through the mediation of e-health literacy. Patient compliance is significantly affected by patient activation. Thus, physicians can achieve higher patient compliance by improving patient activation. Guaranteeing and improving the information quality in OHCs is essential for physicians and OHCs operators. Physicians should pay extra attention in cultivating patients' e-health literacy through communications and health information-seeking behaviors to further improve patient compliance.
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http://dx.doi.org/10.1089/tmj.2019.0258DOI Listing
November 2020

Involvement of the VGF-derived peptide TLQP-62 in nerve injury-induced hypersensitivity and spinal neuroplasticity.

Pain 2018 Sep;159(9):1802-1813

Department of Neuroscience, University of Minnesota, Minneapolis, MN, United States.

Neuroplasticity in the dorsal horn after peripheral nerve damage contributes critically to the establishment of chronic pain. The neurosecretory protein VGF (nonacronymic) is rapidly and robustly upregulated after nerve injury, and therefore, peptides generated from it are positioned to serve as signals for peripheral damage. The goal of this project was to understand the spinal modulatory effects of the C-terminal VGF-derived peptide TLQP-62 at the cellular level and gain insight into the function of the peptide in the development of neuropathic pain. In a rodent model of neuropathic pain, we demonstrate that endogenous levels of TLQP-62 increased in the spinal cord, and its immunoneutralization led to prolonged attenuation of the development of nerve injury-induced hypersensitivity. Using multiphoton imaging of submaximal glutamate-induced Ca responses in spinal cord slices, we demonstrate the ability of TLQP-62 to potentiate glutamatergic responses in the dorsal horn. We further demonstrate that the peptide selectively potentiates responses of high-threshold spinal neurons to mechanical stimuli in singe-unit in vivo recordings. These findings are consistent with a function of TLQP-62 in spinal plasticity that may contribute to central sensitization after nerve damage.
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http://dx.doi.org/10.1097/j.pain.0000000000001277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6095807PMC
September 2018

[α7 nicotinic acetylcholine receptor agonist attenuated the lipopolysaccharide-induced inflammatory response via inhibiting the activation of nuclear factor-ΚB].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2017 Apr;29(4):300-305

Department of Anesthesiology, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, Shanxi, China (Shi XX, Wang C, Zhang XJ); Department of Anesthesiology, Xi'an NO.4 Hospital, Xi'an 710032, Shaanxi, China (Yao JH). Corresponding author: Zhang Xijing, Email:

Objective: To investigate the effects of α7 nicotinic acetylcholine receptor (α7nAChR) on the inflammatory response induced by lipopolysaccharide (LPS) in RAW264.7 macrophages and its molecular mechanisms.

Methods: RAW264.7 macrophages were cultured in vitro. Inflammatory cell model was constructed by LPS stimulation. Cells were challenged by LPS (1, 10, 100 and 500 μg/L) for 5 hours or 100 μg/L LPS for 0, 2, 4, 8, 12, 24, 48 and 72 hours, and the release of tumor necrosis factor-α (TNF-α) was detected by the enzyme linked immunosorbent assay (ELISA). The location of α7nAChR was examined in RAW264.7 macrophages by immunofluorescence. Then the cell proliferation and toxicity kit (CCK-8) was used to detect 1, 10, 100, 1?000 μmol/L GTS-21, a α7nAchR agonist, on the cell viability after LPS stimulation. ELISA was used to detect 1, 10, 100, 1?000 μmol/L GTS-21 on the levels of TNF-α, interleukin 1β (IL-1β) after LPS stimulation. Cells were challenged with 100 ?g/L LPS and 100 ?mol/L GTS-21, then, the level of high mobility group box 1 (HMGB1) was detected by Western Blot and the intracellular location of HMGB1 and nuclear factor-ΚB p65 (NF-ΚB p65) was tested by immunofluorescence.

Results: LPS increased the level of TNF-α to a peak at the concentration of 100 μg/L and at 24 hours after stimulation. The α7nAChR expressed on the macrophages. The cell viability was decreased in a dose-dependent manner [(96.2±1.0)%, (92.0±1.1)% vs. (86.5±2.2)%, both P < 0.05]. Compared with the control group, the levels of TNF-α and IL-1β in the supernatant of LPS group were significantly increased [TNF-α (ng/L): 453.0±60.6 vs. 100.8±3.2, IL-1β (μg/L): 8.21±0.31 vs. 0.87±0.16, both P < 0.05]. TNF-α and IL-1β were significantly decreased by 10 μmol/L and 100 μmol/L GTS-21 in a dose-dependent manner [TNF-α (ng/L): 227.5±17.5, 81.0±8.8 vs. 453.0±60.6; IL-1β (μg/L): 4.86±0.72, 2.32±0.45 vs. 8.21±0.31, all P < 0.05]. GTS-21 significantly reduced the expression of HMGB1 which was induced by LPS management (gray value: 0.788±0.130 vs. 2.061±0.330, P < 0.05) and reversed LPS-induced HMGB1 cytoplasmic transfer. GTS-21 also reversed LPS-induced nuclear translocation of NF-ΚB p65.

Conclusions: GTS-21 reduces the inflammatory response via inhibiting the activation of NF-ΚB.
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http://dx.doi.org/10.3760/cma.j.issn.2095-4352.2017.04.003DOI Listing
April 2017

[Statistics of causes of death and analysis of risk factors in a surgical intensive care unit].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2015 Nov;27(11):880-4

Objective: To summarize the causes of death and to analyze the risk factors in a surgical intensive care unit (SICU).

Methods: The relevant information of patients died in the SICU of Xijing Hospital of Fourth Military Medical University in past 15 years (from December 1999 to February 2015) was retrospectively analyzed. The gender, age, reason and date of hospitalization, date of transfer SICU, past medical history, whether or not admitted directly from emergency department or transferred from other department, operated or not, date of death, the main cause of death, acute physiology and chronic health evaluation II (APACHE II) score, the history of undergoing mechanical ventilation, continuous renal replacement therapy (CRRT), or antifungal therapy, as well as the ratio of the patients with body temperature higher than 39 °C, white blood cell (WBC) count higher than 10 x 10⁹/L, platelet (PLT) count below 100 x 10⁹/L, albumin (Alb) below 35 g/L of two periods, namely from December 1999 to July 2007 (the first period), and from August 2007 to February 2015 (the second period) were compared. The above parameters were compared with those of 201 survivors in SICU, and the risk factors leading to death were analyzed by logistic regression.

Results: From December 1999 to February 2015, 4 317 patients were taken care of in the SICU. Among them, the number of death was 186, and the mortality rate was 4.3%. In the first time period (from December 1999 to July 2007), the total number of patients was 1 356, and the number of death were 109 (the mortality rate was 8.0%). In the second period, i.e. from August 2007 to February 2015, the number of SICU patients was 2,961, and 77 died (the mortality rate was 2.6%). The difference of mortality rate between the two periods was statistically significant (χ² = 66.707, P = 0.001 ). The death rate of patients transferred directly from emergency department in the first period was 79.8% (87/109), and it was lower in the second period (51.9%, 40/77, χ² = 16.181, P = 0.001 ). The death rate of the patients with blood A1b below 35 g/L in the second period (59.7%, 46/77) was higher than that of the first period (41.3%, 45/109, χ² = 6.151, P = 0.017). The top three causes of death from December 1999 to February 2015 were sepsis (38.2%), trauma (16.7%), and operation for cancer (14.0%). In the first period, the top three causes of death were sepsis (35.8%), trauma (22.0%), and operation for cancer (13.8%). In the second period, the top three causes of death were sepsis (41.6%), damage of the central nervous system (16.9%), and operation for cancer (14.3%). Top three reasons for SICU admission were trauma (29.03%), abdominal pain (20.97%) and other reasons (18.82%). Top three departments from which the patients were transferred were the emergency department (19.35%), orthopedics department (17.20%), and hepatobiliary department (16.13%). Logistic regression analysis showed that age [odds ratio (OR) = 2.025, 95% confidence interval (95% CI) = 1.500-2.734, P = 0.000], mechanical ventilation (OR = 3.514, 95% CI = 1.701-7.259, P = 0.001), CRR T (OR = 5.604, 95% CI = 3.003-10.459, P = 0.000 ), body temperature higher than 39 °C (OR = 1.992, 95%CI = 1.052-3.771, P = 0.034) were the risk factors of death in SICU patients.

Conclusion: Sepsis and severe trauma are the leading causes of death in severe SICU patients, to whom with risk factors of death enough attention should be given.
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November 2015

Focal cerebral ischemic tolerance and change in blood-brain barrier permeability after repetitive pure oxygen exposure preconditioning in a rodent model.

J Neurosurg 2016 10 29;125(4):943-952. Epub 2016 Jan 29.

Department of Anesthesiology and.

OBJECTIVE The goal of this study was to demonstrate that repetitive pure oxygen exposure preconditioning (OPC) for 8 hours per day for 3 or 7 days, a practicable preconditioning for clinical use, is able to induce cerebral ischemic tolerance (IT) and further clarify the accompanying changes in the blood-brain barrier (BBB) that may be involved. METHODS A total of 68 adult male Sprague-Dawley rats and eight 1-day-old rat pups were used in this study. The adult rats were exposed to pure O (38 rats) 8 hours a day for 3 or 7 days or to room air (in an identical setup) for 8 hours a day for 7 days as controls (30 rats). Arterial O tension (PaO) was measured in 6 rats exposed to O and 3 controls. Focal cerebral ischemia was elicited by middle cerebral artery occlusion (MCAO) in 37 rats, of which 21 had been exposed to pure O for 3 or 7 days and 16 to room air for 7 days as controls. Neurological behavior was scored with the Garcia score in 15 MCAO rats, of which 10 had been exposed to pure O for 3 or 7 days and 5 to room air for 7 days as controls, and cerebral infarct volumes were assessed with TTC (2,3,5-triphenyltetrazolium chloride) staining in 10 rats (5 from each group) after 7 days of exposure. Formamide-extraction method was used to detect leakage of Evans blue (EB) dye in 7 rats exposed to pure O for 7 days and 7 exposed to room air for 7 days. Fluorescence microscopy was used to analyze the leaked EB in the nonischemic areas of 4 rats exposed to pure O for 7 days and 4 exposed to room air for 7 days before MCAO and the brain of the rats that had not been subjected to MCAO. Astrocyte changes associated with OPC were evaluated by means of fluorescence microscopy and electron microscopy in 14 rats that were exposed to the same O or control conditions as the MCAO rats but without MCAO. Astrocytes were also obtained from 8 rat pups and cultured; levels of AQP4 and VEGF were detected by Western blot and ELISA in cells with and without O treatment. RESULTS A significant increase in PaO was seen after OPC. The neurological score was significantly increased in the OPC groups (10.6 ± 0.6 in the 3-day OPC group, p < 0.05; 12 ± 0.84 in the 7-day OPC group, p < 0.05) compared with the control group (7 ± 0.55). The ratio of cerebral infarct volume to contralateral cerebral hemisphere volume was significantly lower in the OPC group than in the control group (0.204 ± 0.03 vs 0.48 ± 0.05, p < 0.05). The amount of leaked EB in the ischemic cerebral hemisphere was also lower in the O-treated rats than in controls (7.53 ± 1.4 vs 11.79 ± 3.3 μg EB/g brain weight, p < 0.05). However, fluorescence microscopy showed significantly greater BBB permeability in the nonischemic areas in the OPC group than in controls (p < 0.05). More red fluorescence could be observed in the nonischemic areas in both the ipsilateral and contralateral sides of the ischemic brain in the OPC animals than in the nonischemic areas in the corresponding sides of the controls. Further investigation of the effect of the OPC itself on the BBB of rats that were not subjected to MCAO showed that there was no EB leakage in the brain parenchyma in the rats exposed to room air, but some red fluorescence patches were noticed in the normal brain from the rats in the OPC group. Astrocytes, including those from areas around the BBB, were activated in the OPC group. Levels of both aquaporin 4 (AQP4) and vascular endothelial growth factor (VEGF) were significantly increased in cultured astrocytes after OPC. CONCLUSIONS These findings suggest that OPC is able to induce IT, which makes it a strong candidate for clinical use. Moreover, OPC can also promote BBB opening, which may contribute to the induction of IT as well as representing a possible strategy for promoting drug transportation into the CNS. Activated astrocytes are likely to be involved in these processes through astrocyte-derived factors, such as AQP4 and VEGF.
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http://dx.doi.org/10.3171/2015.7.JNS142220DOI Listing
October 2016

Macrophage migration inhibitory factor promotes proliferation and neuronal differentiation of neural stem/precursor cells through Wnt/β-catenin signal pathway.

Int J Biol Sci 2013 28;9(10):1108-20. Epub 2013 Nov 28.

1. Department of Anesthesiology, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, China.

Macrophage migration inhibitory factor (MIF) is a highly conserved and evolutionarily ancient mediator with pleiotropic effects. Recent studies demonstrated that the receptors of MIF, including CD44, CXCR2, CXCR4 and CD74, are expressed in the neural stem/progenitor cells (NSPCs). The potential regulatory effect of MIF on NSPCs proliferation and neuronal differentiation, however, is largely unknown. Here, we investigated the effect of MIF on NSPC proliferation and neuronal differentiation, and further examined the signal pathway by which MIF transduced these signal effects in mouse NSPCs in vitro. The results showed that both Ki67-positive cells and neurosphere volumes were increased in a dose-dependent manner following MIF treatment. Furthermore, the expression of nuclear β-catenin was significantly stronger in MIF-stimulated groups than that in control groups. Conversely, administration of IWR-1, the inhibitor of Wnt/β-catenin pathway, significantly inhibited the proliferative effect of MIF on NSPCs. Immunostaining and Western blot further indicated that doublecortin (DCX) and Tuj 1, two neuronal markers, were evidently increased with MIF stimulation during NSPC differentiation, and there were more Tuj1-positive cells migrated out from neurospheres in MIF-stimulated groups than those in control groups. During NSPC differentiation, MIF increased the activity of β-galactosidase that responds to Wnt/β-catenin signaling. Wnt1 and β-catenin proteins were also up-regulated with MIF stimulation. Moreover, the expression of DCX and Tuj 1 was inhibited significantly by IWR-1. Taken together, the present study indicated that MIF enhances NSPC proliferation and promotes the neuronal differentiation, by activating Wnt/β-catenin signal pathway. The interaction between MIF and Wnt/β-catenin signal pathway may play an important role in modulating NSPC renewal and fate during brain development.
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http://dx.doi.org/10.7150/ijbs.7232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858584PMC
July 2014

Involvement of α7 nAChR signaling cascade in epigallocatechin gallate suppression of β-amyloid-induced apoptotic cortical neuronal insults.

Mol Neurobiol 2014 Feb 27;49(1):66-77. Epub 2013 Jun 27.

Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, China.

Excessive generation and accumulation of the β-amyloid (Aβ) peptide in selectively vulnerable brain regions is a key pathogenic event in the Alzheimer's disease (AD), while epigallocatechin gallate (EGCG) is a very promising chemical to suppress a variety of Aβ-induced neurodegenerative disorders. However, the precise molecular mechanism of EGCG responsible for protection against neurotoxicity still remains elusive. To validate and further investigate the possible mechanism involved, we explored whether EGCG neuroprotection against neurotoxicity of Aβ is mediated through the α7 nicotinic acetylcholine receptor (α7 nAChR) signaling cascade. It was shown in rat primary cortical neurons that short-term treatment with EGCG significantly attenuated the neurotoxicity of Aβ1-42, as demonstrated by increased cell viability, reduced number of apoptotic cells, decreased reactive oxygen species (ROS) generation, and downregulated caspase-3 levels after treatment with 25-μM Aβ1-42. In addition, EGCG markedly strengthened activation of α7nAChR as well as its downstream pathway signaling molecules phosphatidylinositol 3-kinase (PI3K) and Akt, subsequently leading to suppression of Bcl-2 downregulation in Aβ-treated neurons. Conversely, administration of α7nAChR antagonist methyllycaconitine (MLA; 20 μM) to neuronal cultures significantly attenuated the neuroprotection of EGCG against Aβ-induced neurototoxicity, thus presenting new evidence that the α7nAChR activity together with PI3K/Akt transduction signaling may contribute to the molecular mechanism underlying the neuroprotective effects of EGCG against Aβ-induced cell death.
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http://dx.doi.org/10.1007/s12035-013-8491-xDOI Listing
February 2014

Self-reported use of personal protective equipment among Chinese critical care clinicians during 2009 H1N1 influenza pandemic.

PLoS One 2012 5;7(9):e44723. Epub 2012 Sep 5.

Peking Union Medical College Hospital, Beijing, People's Republic of China.

Background: Critically ill patients with 2009 H1N1 influenza are often treated in intensive care units (ICUs), representing significant risk of nosocomial transmission to critical care clinicians and other patients. Despite a large body of literature and guidelines recommending infection control practices, numerous barriers have been identified in ICUs, leading to poor compliance to the use of personal protective equipment (PPE). The use of PPE among critical care clinicians has not been extensively evaluated, especially during the pandemic influenza. This study examined the knowledge, attitudes, and self-reported behaviors, and barriers to compliance with the use of PPE among ICU healthcare workers (HCWs) during the pandemic influenza.

Methodology/principal Findings: A survey instrument consisting of 36 questions was developed and mailed to all HCWs in 21 ICUs in 17 provinces in China. A total of 733 physicians, nurses, and other professionals were surveyed, and 650 (88.7%) were included in the analysis. Fifty-six percent of respondents reported having received training program of pandemic influenza before they cared for H1N1 patients, while 77% reported to have adequate knowledge of self and patient protection. Only 18% of respondents were able to correctly identify all components of PPE, and 55% reported high compliance (>80%) with PPE use during patient care. In multivariate analysis, vaccination for 2009 H1N1 influenza, positive attitudes towards PPE use, organizational factors such as availability of PPE in ICU, and patient information of influenza precautions, as well as reprimand for noncompliance by the supervisors were associated with high compliance, whereas negative attitudes towards PPE use and violation of PPE use were independent predictors of low compliance.

Conclusion/significance: Knowledge and self-reported compliance to recommended PPE use among Chinese critical care clinicians is suboptimal. The perceived barriers should be addressed in order to close the significant gap between perception and knowledge or behavior.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0044723PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3434157PMC
February 2013

Pruriceptive spinothalamic tract neurons: physiological properties and projection targets in the primate.

J Neurophysiol 2012 Sep 20;108(6):1711-23. Epub 2012 Jun 20.

Dept. of Neuroscience, Univ. of Minnesota, Minneapolis, MN 55455, USA.

Itch of peripheral origin requires information transfer from the spinal cord to the brain for perception. Here, primate spinothalamic tract (STT) neurons from lumbar spinal cord were functionally characterized by in vivo electrophysiology to determine the role of these cells in the transmission of pruriceptive information. One hundred eleven STT neurons were identified by antidromic stimulation and then recorded while histamine and cowhage (a nonhistaminergic pruritogen) were sequentially applied to the cutaneous receptive field of each cell. Twenty percent of STT neurons responded to histamine, 13% responded to cowhage, and 2% responded to both. All pruriceptive STT neurons were mechanically sensitive and additionally responded to heat, intradermal capsaicin, or both. STT neurons located in the superficial dorsal horn responded with greater discharge and longer duration to pruritogens than STT neurons located in the deep dorsal horn. Pruriceptive STT neurons discharged in a bursting pattern in response to the activating pruritogen and to capsaicin. Microantidromic mapping was used to determine the zone of termination for pruriceptive STT axons within the thalamus. Axons from histamine-responsive and cowhage-responsive STT neurons terminated in several thalamic nuclei including the ventral posterior lateral, ventral posterior inferior, and posterior nuclei. Axons from cowhage-responsive neurons were additionally found to terminate in the suprageniculate and medial geniculate nuclei. Histamine-responsive STT neurons were sensitized to gentle stroking of the receptive field after the response to histamine, suggesting a spinal mechanism for alloknesis. The results show that pruriceptive information is encoded by polymodal STT neurons in histaminergic or nonhistaminergic pathways and transmitted to the ventrobasal complex and posterior thalamus in primates.
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http://dx.doi.org/10.1152/jn.00206.2012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544948PMC
September 2012

MIF produced by bone marrow-derived macrophages contributes to teratoma progression after embryonic stem cell transplantation.

Cancer Res 2012 Jun 29;72(11):2867-78. Epub 2012 Mar 29.

W. M. Keck Center for Collaborative Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.

Although stem cell therapy holds promise as a potential treatment in a number of diseases, the tumorigenicity of embryonic stem cells (ESC) and induced pluripotent stem cells remains a major obstacle. In vitro predifferentiation of ESCs can help prevent the risk of teratoma formation, yet proliferating neural progenitors can generate tumors, especially in the presence of immunosuppressive therapy. In this study, we investigated the effects of the microenvironment on stem cell growth and teratoma development using undifferentiated ESCs. Syngeneic ESC transplantation triggered an inflammatory response that involved the recruitment of bone marrow (BM)-derived macrophages. These macrophages differentiated into an M2 or angiogenic phenotype that expressed multiple angiogenic growth factors and proteinases, such as macrophage migration inhibitory factor (MIF), VEGF, and matrix metalloproteinase 9, creating a microenvironment that supported the initiation of teratoma development. Genetic deletion of MIF from the host but not from ESCs specifically reduced angiogenesis and teratoma growth, and MIF inhibition effectively reduced teratoma development after ESC transplantation. Together, our findings show that syngeneic ESC transplantation provokes an inflammatory response that involves the rapid recruitment and activation of BM-derived macrophages, which may be a crucial driving force in the initiation and progression of teratomas.
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http://dx.doi.org/10.1158/0008-5472.CAN-11-3247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3779606PMC
June 2012

TREK1 activation mediates spinal cord ischemic tolerance induced by isoflurane preconditioning in rats.

Neurosci Lett 2012 May 10;515(2):115-20. Epub 2012 Mar 10.

Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.

The aim of this study is to examine the role of one of the two-pore (2P) domain K(+) channels, TREK (TWIK-related K(+) channels, TREK)-1, mediated neuroprotection on spinal cord afforded by isoflurane preconditioning. In Experiment 1, male Sprague-Dawley rats were randomly assigned to control (Con) group, an isoflurane preconditioning (Iso) group, and sham group. Twenty-four hours after the last pretreatment, spinal cord ischemia was induced in Con and Iso groups. Neurobehavioral testing and histopathologic examination were performed after reperfusion. In Experiment 2, the expression of the TREK1 in the spinal cord was assessed by immunohistochemistry, Western blot and real-time polymerase chain reaction. In Experiment 3, Amiloride, a blocker of stretch-sensitive channels, was administered intraperitoneally immediately prior to each isoflurane preconditioning. Iso group showed a significant reductions in motor deficit index as well as increases in the number of normal neurons compared with the Con group. The expression of TREK1 protein and the level of mRNA after ischemia were higher in the rats of the Iso group than those in the Con group. Amiloride pretreatment abolished the protective effects of Iso preconditioning. These finding indicate that isoflurane preconditioning had a neuroprotective effect against spinal cord ischemia reperfusion injury. These effects may be mediated through the TREK1 pathway.
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http://dx.doi.org/10.1016/j.neulet.2012.03.006DOI Listing
May 2012

Knowledge and attitudes of healthcare workers in Chinese intensive care units regarding 2009 H1N1 influenza pandemic.

BMC Infect Dis 2011 Jan 25;11:24. Epub 2011 Jan 25.

The First Affiliated Hospital of China Medical University, Shenyang, PR China.

Background: To describe the knowledge and attitudes of critical care clinicians during the 2009 H1N1 influenza pandemic.

Methods: A survey conducted in 21 intensive care units in 17 provinces in China.

Results: Out of 733 questionnaires distributed, 695 were completed. Three hundred and fifty-six respondents (51.2%) reported their experience of caring for H1N1 patients. Despite the fact that 88.5% of all respondents ultimately finished an H1N1 training program, only 41.9% admitted that they had the knowledge of 2009 H1N1 influenza. A total of 572 respondents (82.3%) expressed willingness to care for H1N1 patients. Independent variables associated with increasing likelihood to care for patients in the logistic regression analysis were physicians or nurses rather than other professionals (odds ratio 4.056 and 3.235, p = 0.002 and 0.007, respectively), knowledge training prior to patient care (odds ratio 1.531, p = 0.044), and the confidence to know how to protect themselves and their patients (odds ratio 2.109, p = 0.001).

Conclusion: Critical care clinicians reported poor knowledge of H1N1 influenza, even though most finished a relevant knowledge training program. Implementation of appropriate education program might improve compliance to infection control measures, and willingness to work in a pandemic.
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http://dx.doi.org/10.1186/1471-2334-11-24DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037318PMC
January 2011

Novel immunohistochemical monoclonal antibody against human XBP-1.

Hybridoma (Larchmt) 2010 Oct;29(5):441-5

Department of Operative Dentistry and Endodontics, School of Stomatology, Fourth Military Medical University, and Department of Respiration, Xijing Hospital, Xi'an, Shaanxi, China.

The X-box binding protein-1(XBP-1) is a 29 kDa protein belonging to the basic region/leucine zipper (bZIP) family of transcription factors. Previous studies showed that XBP-1 mediated a wide range of responses in B-cell differentiation, unfolded protein response (UPR), and tumorigenesis. For these reasons, it is believed that XBP-1 would be a novel therapeutic target in some pathogenic processes. In this study, a set of XBP-1 MAbs were raised and cloned. Then it was proven that some clones among them could be used in Western blot analysis, immunocytochemistry, or immunohistochemistry. Therefore, the obtained MAbs not only provided new powerful tools for investigation of expression profile and functions of XBP-1 protein, but also provided the possibility of generating gene engineering antibodies specific for targeting XBP-1.
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http://dx.doi.org/10.1089/hyb.2010.0030DOI Listing
October 2010

Cannabinoid 1 receptor mediation of spinal cord ischemic tolerance induced by limb remote ischemia preconditioning in rats.

J Thorac Cardiovasc Surg 2009 Dec 25;138(6):1409-16. Epub 2009 Aug 25.

Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.

Objective: The aim of this study was to examine the influence of endogenous cannabinoids on neuroprotection of the spinal cord afforded by limb remote ischemic preconditioning.

Methods: In experiment 1 (RIPC group), 3 cycles of limb remote ischemic preconditioning within different episodes (2, 3, or 5 minutes) were induced before spinal cord ischemia in rats (N = 5, n = 8). In experiment 2, animals were pretreated intravenously by the vehicles, cannabinoid 1 (AM251, 1 mg/kg) or cannabinoid 2 (AM630, 1 mg/kg) receptor antagonist 15 minutes before remote ischemic preconditioning, or else they were subjected to a sham operation. Thirty minutes after the pretreatment, spinal cord ischemia was induced (N = 8, n = 8). In experiment 3, the arachidonylethanolamide and 2-arachidonoylglycerol contents in the spinal cord after remote ischemic preconditioning and spinal cord ischemia were detected in rats (N = 2, n = 12). Spinal cord ischemia was induced by 12 minutes of thoracic aorta occlusion in rats. Neurologic function was assessed 24 and 48 hours after reperfusion. Histopathologic examination was performed and the number of normal neurons in anterior spinal cord were counted.

Results: In experiment 1, 3 cycles of limb remote ischemic preconditioning (3 minutes of ischemia/3 minutes of reperfusion) induced ischemic tolerance on the spinal cords of the rats. The RIPC group showed a significant reduction in motor deficit index (P < .01) as well as an increase in the number of normal neurons (P < .01). In experiment 2, the cannabinoid 1 receptor antagonist AM251 pretreatment abolished the protective effects of remote preconditioning. In experiment 3, arachidonylethanolamide content in spinal cord was elevated by remote ischemic preconditioning in rats.

Conclusion: These results indicated that endogenous cannabinoids, through acting on cannabinoid 1 receptors, were involved in the neuroprotective phenomenon on spinal cords of limb remote ischemic preconditioning.
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http://dx.doi.org/10.1016/j.jtcvs.2009.07.014DOI Listing
December 2009

Relief of itch by scratching: state-dependent inhibition of primate spinothalamic tract neurons.

Nat Neurosci 2009 May 6;12(5):544-6. Epub 2009 Apr 6.

University of Minnesota, Minneapolis, USA.

Itch is relieved by scratching, but the neural mechanisms that are responsible for this are unknown. Spinothalamic tract (STT) neurons respond to itch-producing agents and transmit pruritic information to the brain. We observed that scratching the cutaneous receptive field of primate STT neurons produced inhibition during histamine-evoked activity but not during spontaneous activity or activity evoked by a painful stimulus, suggesting that scratching inhibits the transmission of itch in the spinal cord in a state-dependent manner.
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http://dx.doi.org/10.1038/nn.2292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3006451PMC
May 2009

Quantification of functional groups and modeling of their ionization behavior in the active layer of FT30 reverse osmosis membrane.

Environ Sci Technol 2008 Jul;42(14):5260-6

Department of Civil and Environmental Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.

A new experimental approach was developed to measure the concentration of charged functional groups (FGs) in the active layer of thin-film composite reverse osmosis (RO) and nanofiltration (NF) membranes as a function of solution pH. FT30 RO membrane, with a fully aromatic polyamide (PA) active layer sandwiched between a polysulfone support and a coating layer, was used. The experiments consisted of saturating charged FGs with heavy ion probes, and determining the ion probe concentration by Rutherford backscattering spectrometry (RBS). Deprotonated carboxylic groups were saturated with Ag+, and protonated amine groups with W04(2-). The ionization behavior of carboxylic and amine groups was modeled based on acid-base equilibrium theory. While the ionization behavior of amine groups was satisfactorily described by one dissociation constant (pKa = 4.74), two pKa values (5.23 and 8.97) were necessary to describe the titration curve of carboxylic groups. These results were consistent with the bimodal pore size distribution (PSD) of FT30 active layer reported in the literature. The calculated total concentrations of carboxylic and amine groups in the active layer of the FT30 RO membrane studied were 0.432 and 0.036 M, respectively, and the isoelectric point (IEP) was 4.7. The total concentration of carboxylic and amine groups revealed that the degree of cross-linking of the PA active layer of the FT30 RO membrane studied was 94%.
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http://dx.doi.org/10.1021/es8002712DOI Listing
July 2008

Termination zones of functionally characterized spinothalamic tract neurons within the primate posterior thalamus.

J Neurophysiol 2008 Oct 13;100(4):2026-37. Epub 2008 Aug 13.

Department of Neuroscience, School of Medicine, University of Minnesota, 6-145 Jackson Hall, 321 Church St. SE, Minneapolis, MN, USA.

The primate posterior thalamus has been proposed to contribute to pain sensation, but its precise role is unclear. This is in part because spinothalamic tract (STT) neurons that project to the posterior thalamus have received little attention. In this study, antidromic mapping was used to identify individual STT neurons with axons that projected specifically to the posterior thalamus in Macaca fascicularis. Each axon was located by antidromic activation at low stimulus amplitudes (<30 microA) and was then surrounded distally by a grid of stimulating points in which 500-microA stimuli were unable to activate the axon antidromically, thereby indicating the termination zone. Several nuclei within the posterior thalamus were targets of STT neurons: the posterior nucleus, suprageniculate nucleus, magnocellular part of the medial geniculate nucleus, and limitans nucleus. STT neurons projecting to the ventral posterior inferior nucleus were also studied. Twenty-five posterior thalamus-projecting STT neurons recorded in lumbar spinal cord were characterized by their responses to mechanical, thermal, and chemical stimuli. Sixteen of 25 neurons were recorded in the marginal zone and the balance was located within the deep dorsal horn. Thirteen neurons were classified as wide dynamic range and 12 as high threshold. One-third of STT neurons projecting to posterior thalamus responded to noxious heat (50 degrees C). Two-thirds of those tested responded to cooling. Seventy-one percent responded to an intradermal injection of capsaicin. These data indicate that the primate STT transmits noxious and innocuous mechanical, thermal, and chemical information to multiple posterior thalamic nuclei.
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http://dx.doi.org/10.1152/jn.90810.2008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2576190PMC
October 2008

The itch-producing agents histamine and cowhage activate separate populations of primate spinothalamic tract neurons.

J Neurosci 2007 Sep;27(37):10007-14

Department of Neuroscience, Medical School, University of Minnesota, Minneapolis, Minnesota 55455, USA.

Itch is an everyday sensation, but when associated with disease or infection it can be chronic and debilitating. Several forms of itch can be blocked using antihistamines, but others cannot and these constitute an important clinical problem. Little information is available on the mechanisms underlying itch that is produced by nonhistaminergic mechanisms. We examined the responses of spinothalamic tract neurons to histaminergic and, for the first time, nonhistaminergic forms of itch stimuli. Fifty-seven primate spinothalamic tract (STT) neurons were identified using antidromic activation techniques and examined for their responses to histamine and cowhage, the nonhistaminergic itch-producing spicules covering the pod of the legume Mucuna pruriens. Each examined neuron had a receptive field on the hairy skin of the hindlimb and responded to noxious mechanical stimulation. STT neurons were tested with both pruritogens applied in a random order and we found 12 that responded to histamine and seven to cowhage. Each pruritogen-responsive STT neuron was activated by the chemical algogen capsaicin and two-thirds responded to noxious heat stimuli, demonstrating that these neurons convey chemical, thermal, and mechanical nociceptive information as well. Histamine or cowhage responsive STT neurons were found in both the marginal zone and the deep dorsal horn and were classified as high threshold and wide dynamic range. Unexpectedly, histamine and cowhage never activated the same cell. Our results demonstrate that the spinothalamic tract contains mutually exclusive populations of neurons responsive to histamine or the nonhistaminergic itch-producing agent cowhage.
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http://dx.doi.org/10.1523/JNEUROSCI.2862-07.2007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3008349PMC
September 2007

Measurements of interface stress of silicon dioxide in contact with water-phenol mixtures by bending of microcantilevers.

Langmuir 2006 Oct;22(21):9062-6

Center of Advanced Materials for the Purification of Water with Systems, Department of Materials Science and Engineering, University of Illinois, Urbana, Illinois 61801, USA.

We use the bending of silicon microcantilevers to measure changes in mechanical stress at interfaces between phenol-water mixtures and SiO(2). The curvature of the microcantilever is measured by an optical system that combines a rapidly scanning laser beam, a position-sensitive detector, and lock-in detection to achieve a long-time stability on the order of 6 mN m(-1) over 4 h and a short-time sensitivity of better than 1 mN m(-1). Thermally oxidized Si shows the smallest changes in interface stress as a function of phenol concentration in water. For hydrophilic SiO(2) prepared by chemical treatment, the change in interface stress at 5 wt % phenol in water is larger than that of thermally oxidized Si by -60 mN m(-1); for SiO(2) formed by exposure of the silicon microcantilever to ozone, the change in surface stress is larger than that of thermally oxidized Si by -330 mN m(-1).
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http://dx.doi.org/10.1021/la061032oDOI Listing
October 2006

Thermally identified subgroups of marginal zone neurons project to distinct regions of the ventral posterior lateral nucleus in rats.

J Neurosci 2006 May;26(19):5215-23

Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455, USA.

Spinal marginal zone (MZ) neurons play a crucial role in the transmission of nociceptive and thermoreceptive information to the brain. The precise areas to which physiologically characterized MZ neurons project in the ventral posterior lateral (VPL) nucleus of the thalamus have not been clearly established. Here, we examine this projection in rats using the method of antidromic activation to map the axon terminals of neurons recorded from the MZ. Thirty-three neurons were antidromically activated using pulses of < or =30 microA in the contralateral VPL. In every case, the most rostral point from which the MZ neuron could be antidromically activated was surrounded by stimulating tracks in which large-amplitude current pulses failed to activate the examined neuron, indicating the termination of the spinothalamic tract (STT) axon. Each of 30 examined neurons responded to noxious but not innocuous mechanical stimuli applied to their cutaneous receptive fields, which ranged in size from two digits to the entire limb. Of 17 thermally tested neurons, 16 responded to innocuous or noxious thermal stimuli. Among STT neurons that responded to thermal stimuli, 50% responded to innocuous cooling as well as noxious heat and cold, 31% responded to noxious heat and cold, and 19% responded only to noxious heat. Axons from cells responsive to innocuous cooling terminated in the core region of VPL, significantly dorsal and medial relative to other thermally responsive subgroups. In rats, thermally responsive subgroups of MZ neurons project directly to distinct regions of VPL.
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http://dx.doi.org/10.1523/JNEUROSCI.0701-06.2006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6674258PMC
May 2006

Response characterstics of spinothalamic tract neurons that project to the posterior thalamus in rats.

J Neurophysiol 2005 May;93(5):2552-64

Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.

A sizeable number of spinothalamic tract axons terminate in the posterior thalamus. The functional roles and precise areas of termination of these axons have been a subject of recent controversy. The goals of this study were to identify spinothalamic tract neurons (STT) within the cervical enlargement that project to this area, characterize their responses to mechanical and thermal stimulation of their receptive fields, and use microantidromic tracking methods to determine the nuclei in which their axons terminate. Forty-seven neurons were antidromically activated using low-amplitude (< or =30 microA) current pulses in the contralateral posterior thalamus. The 51 points at which antidromic activation thresholds were lowest were surrounded by ineffective tracks indicating that the surrounded axons terminated within the posterior thalamus. The areas of termination were located primarily in the posterior triangular, medial geniculate, posterior and posterior intralaminar, and suprageniculate nuclei. Recording points were located in the superficial and deep dorsal horn. The mean antidromic conduction velocity was 6.4 m/s, a conduction velocity slower than that of other projections to the thalamus or hypothalamus in rats. Cutaneous receptive fields appeared to be smaller than those of neurons projecting to other areas of the thalamus or to the hypothalamus. Each of the examined neurons responded exclusively or preferentially to noxious stimuli. These findings indicate that the STT carries nociceptive information to several target nuclei within the posterior thalamus. We discuss the evidence that this projection provides nociceptive information that plays an important role in fear conditioning.
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http://dx.doi.org/10.1152/jn.01237.2004DOI Listing
May 2005

Preconditioning with prolonged oxygen exposure induces ischemic tolerance in the brain via oxygen free radical formation.

Can J Anaesth 2004 Mar;51(3):258-63

Department of Anesthesiology, Xijing Hospital, Xi'an, Shaanxi, China.

Purpose: To determine if 100% oxygen (O2) inhalation induces ischemic tolerance to focal cerebral ischemia and if the effect is induced via O2 free radical formation.

Methods: Experiment 1: 36 rats were randomly assigned to four groups (n = 9 each): Group A, control rats inhaled air for 24 hr; Groups B, C and D animals inhaled 100% O2 for six hours, 12 hr and 24 hr respectively. Experiment 2: 32 rats were randomly assigned to four groups (n = 8 each): Groups E and F rats received normal saline (5 mL.kg(-1) intraperitoneally) and then inhaled air (Group E) or 100% O2 (Group F) for 24 hr; Groups G and H animals received 10% dimethylthiourea (500 mg.kg(-1) intraperitoneally) and then inhaled 100% O2 (Group G) or air (Group H) for 24 hr. Twenty-four hours after the treatments, the right middle cerebral artery was occluded in all rats for 120 min. The neurologic deficit scores (NDS) and brain infarct volumes were evaluated at 24 hr after reperfusion.

Results: Experiment 1: the infarct volume and NDS of Group D were smaller than in controls (P = 0.004 and 0.042 respectively). The infarct volume was reduced by 47% in Group D. There was no statistical difference among Groups A, B and C. Experiment 2: the infarct volume and NDS in Group F were less than in controls (Group E; P = 0.001 and 0.036 respectively). The infarct volume was reduced by 60% in Group F. There was no difference among Groups E, G and H.

Conclusion: Our study demonstrates that preconditioning with 100% O2 for 24 hr can induce ischemic tolerance via formation of O2 free radicals in transient focal cerebral ischemia in rats.
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http://dx.doi.org/10.1007/BF03019107DOI Listing
March 2004