Publications by authors named "Mina Ranjbaran"

36 Publications

Tannic acid protects aged brain against cerebral hypoperfusion via modulation of Nrf2 and inflammatory pathways.

Neurosci Lett 2021 Sep 22;765:136263. Epub 2021 Sep 22.

Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran; Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Current study purposed to investigate the neuroprotective effects of Tannic Acid (TA) on mild chronic cerebral hypoperfusion model in rats. Male Wistar rats were subjected to permanent Unilateral Common Carotid Artery Occlusion (UCCAO), followed by TA treatment (0.05% w/v) in drinking water for one month. Nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H: quinone oxidoreductase 1 (NQO-1), heme oxygenase-1 (HO-1), factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor-α (TNF-α), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3, blood triglyceride, blood glucose, and liver enzymes' activity were detected after the experimental period. Also, behavioral tests, hematoxylin and eosin (H&E) staining, and PET scan were performed after treatment. Post-treatment of TA improved locomotion and memory function (P < 0.001), and reduced neural cell death (P < 0.001) in the treatment group compared to UCCAO rats. Furthermore, long-term TA treatment significantly increased the levels of Nrf2 (P < 0.001), NQO-1 (P < 0.001), and HO-1 (P < 0.001) in the hippocampus of the treatment group compared to the UCCAO group. TA consumption in the treatment group applied its anti-inflammatory effects via reducing the activity of NF-κB and TNF-α in comparison with the UCCAO group (P < 0.001 for both). Blood triglyceride, blood glucose, and liver enzymes did not change considerably in the groups (P > 0.05). The current results indicate that long-term post-treatment of TA exhibits protective effects against memory deficit and motor dysfunction. The cellular mechanism of TA in hypoperfused rats might be associated with the activation of antioxidant pathways, especially the Nrf2 pathway, and suppressing inflammatory factors like NF-κB and TNF-α.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neulet.2021.136263DOI Listing
September 2021

Therapeutic Effects of Resveratrol on Ischemia-Reperfusion Injury in the Nervous System.

Neurochem Res 2021 Dec 7;46(12):3085-3102. Epub 2021 Aug 7.

Department of Biochemistry, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Resveratrol is a phenol compound produced by some plants in response to pathogens, infection, or physical injury. It is well-known that resveratrol has antioxidant and protective roles in damages potentially caused by cancer or other serious disorders. Thus, it is considered as a candidate agent for the prevention and treatment of human diseases. Evidence has confirmed other bioactive impacts of resveratrol, including cardioprotective, anti-tumorigenic, anti-inflammatory, phytoestrogenic, and neuroprotective effects. Ischemia-reperfusion (IR) can result in various disorders, comprising myocardial infarction, stroke, and peripheral vascular disease, which may continue to induce debilitating conditions and even mortality. In virtue of chronic ischemia or hypoxia, cells switch to anaerobic metabolism, giving rise to some dysfunctions in mitochondria. As the result of lactate accumulation, adenosine triphosphate levels and pH decline in cells. This condition leads cells to apoptosis, necrosis, and autophagy. However, restoring oxygen level upon reperfusion after ischemia by producing reactive oxygen species is an outcome of mitochondrial dysfunction. Considering the neuroprotective effect of resveratrol and neuronal injury that comes from IR, we focused on the mechanism(s) involved in IR injury in the nervous system and also on the functions of resveratrol in the protection, inhibition, and treatment of this injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11064-021-03412-zDOI Listing
December 2021

Dimethyl fumarate protects the aged brain following chronic cerebral hypoperfusion-related ischemia in rats in Nrf2-dependent manner.

Nutr Neurosci 2021 Jun 19:1-11. Epub 2021 Jun 19.

Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

It has been stated that chronic cerebral hypoperfusion (CCH) markedly prompts neuronal damage and affects cognition. Dimethyl fumarate (DMF), a nuclear erythroid 2-related factor 2 (Nrf2) activator, represents a class of molecules exhibiting neuroprotection. We explored the effect of DMF on CCH using a model of permanent left common carotid occlusion. The left common carotid artery was occluded and then DMF (100mg.kg) was orally administrated three times per week for four consecutive weeks. Behavioral rests, PET imaging and Hematoxylin and Eosin staining, were examined and also, the hippocampal level of inflammatory, Nrf2 antioxidant, neuronal plasticity and apoptotic factors were determined using Western blot analysis and related ELISA kits. The neurological deficit scores were significantly reduced in the treatment group compared with the CCH group (<0.001). DMF decreased the novel object recognition index (NOR) compared with the CCH group, while CCH + DMF increased the NOR compared with the CCH group (<0.001). CCH + DMF reduces the ratio of Bax/Bcl2 and capase-3 activity in comparison to the CCH group (<0.001). Treatment with DMF increased Nrf2, NAD(P)H dehydrogenase-1 and Heme oxygenase-1 and decreased Tumor necrosis factor α and Nuclear factor-κB density compared with the CCH group (<0.001). A significant increase in brain-derived neurotrophic factor and c-fos was found in DMF-treated rats compared with the CCH group (<0.001). Also, retinoic acid inhibits Nrf2 activation via DMF and increases inflammatory factors in hypoperfused rats' hippocampus compared with the CCH group (<0.001). Long-term DMF treatment induces the Nrf2 pathway and has beneficial effects on memory and motility in CCH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/1028415X.2021.1940429DOI Listing
June 2021

Role of the mesenchymal stem cells derived from adipose tissue in changing the rate of breast cancer cell proliferation and autophagy, and .

Iran J Basic Med Sci 2021 Jan;24(1):98-107

Abadan Faculty of Medical Science, Abadan, Iran.

Objectives: Autophagy is an intracellular degradation system of damaged proteins and organelles; however, the role of autophagy in the progression of cancer remains unclear. In recent years, mesenchymal stem cell (MSC)-based approaches have attracted considerable attention for anti-cancer therapy. The present study aimed to examine the interaction of MSCs with the breast cancer cells under autophagy-induced conditions.

Materials And Methods: In this study, MSCs isolated from human adipose tissue were co-cultured with MDA-MB 231, a breast cancer cell line, and the autophagy process was induced by tunicamycin treatment. The cell viability was monitored by the MTT assay, and the cells were recovered at different time intervals (24 or 48 hours) to determine autophagy markers such as Beclin, mTOR and the ratio of LC3II/I expression. Additionally, the animal study was conducted using a mouse model of breast cancer treated with isogenic adipose-derived MSCs, and the expression of Beclin and Ki67 was determined using immunohistochemistry in breast tumor tissue.

Results: In cancer cells co-cultured with MSCs, the cell proliferation was increased, the Beclin expression and the LC3II/I protein ratio were decreased, and the mTOR expression was increased in MDA-MB 231 upon co-cultured with MSCs. Direct injection of MSCs to a mouse model of breast cancer showed an increase in tumor volume, an increase in the accumulation of Ki67 and a decrease in the Beclin expression in tumor tissues.

Conclusion: The data may suggest that suppressed autophagy in breast cancer cells is probably a mechanism by which MSCs can induce cancer cell proliferation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.22038/ijbms.2020.51461.11678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894629PMC
January 2021

Nephroprotection through Modifying the Apoptotic TNF-α/ERK1/2/Bax Signaling Pathway and Oxidative Stress by Long-term Sodium Hydrosulfide Administration in Ovalbumin-induced Chronic Asthma.

Immunol Invest 2020 Dec 21:1-17. Epub 2020 Dec 21.

Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Asthma is one of the most common respiratory diseases in the world. Nevertheless, it is reported that inflammation induced by asthma is not only restricted to the lung and may cause damaging effects on remote organs. Therefore, this study was designed to investigate the beneficial effects of long-term sodium hydrosulfide (NaHS) administration on lung inflammation and oxidative stress markers to protect the kidney during chronic asthma. BALB/c mice were divided into three groups ( = 5-7): control, asthma and NaHS. Except the control group, sensitization and challenge were performed with ovalbumin. The NaHS group intraperitoneally received 14 μmol/kg NaHS 30 min before each challenge. 24 h after the last challenge, samples of bronchoalveolar lavage fluid (BALF), plasma, lung and kidney tissues were collected. NaHS administration significantly decreased total white blood cell count, percentages of eosinophils, neutrophils and macrophages and increased percentage of lymphocytes. Administration of NaHS considerably decreased the levels of BALF interleukin-13, plasma tumor necrosis factor-alpha (TNF-α), lung malondialdehyde (MDA) and lung phosphorylated nuclear factor-kappa B (-NF-κB) expression and scores of peribronchial inflammatory cell infiltration, goblet cell hyperplasia and subepithelial fibrosis and increased the activity of lung superoxide dismutase (SOD). The MDA levels and expressions of -ERK1/2 and Bax were decreased and SOD activity and expressions of Bcl-2 and -Akt were significantly increased in kidney tissues by NaHS administration. Administration of NaHS decreased renal oxidative stress indices and reduced apoptosis by the inhibition of TNF-α/ERK1/2/Bax. Therefore, HS may have an essential role in renal protection during asthma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/08820139.2020.1858860DOI Listing
December 2020

High-protein and low-calorie diets improved the anti-aging Klotho protein in the rats' brain: the toxic role of high-fat diet.

Nutr Metab (Lond) 2020 15;17:86. Epub 2020 Oct 15.

Department of Physiology, School of Medicine, Tehran University of Medical Sciences, P.O.box: 1417613151, Tehran, Iran.

Background: In the current study, our specific aim was to characterize the Klotho protein and expression levels in the hippocampus and prefrontal cortex of old rats treated with different diets (high-fat, high-protein, low-calorie, high-protein and low-calorie).

Methods: Rats were treated with high-fat, high-protein, low-calorie, low-calorie high-protein diets for 10 weeks and then behavioral and molecular assessments were evaluated.

Results: Statistical analysis showed the percentage of open arm time was increased in the high-protein, low-calorie and low-calorie high-protein groups compared with old control (old-C) rats. The percentage of open arm entries was increased in the low-calorie and low-calorie high-protein group compared with old-C rats. The body weight and serum triglyceride were decreased in the low-calorie and low-calorie high-protein groups in comparison to control old rats. Low-calorie and low-calorie high-protein treatments statistically enhanced caspase-3 level compared with old-C rats in the hippocampus and prefrontal cortex. Treatment of old rats with high-protein, low-calorie and low-calorie high-protein could increase Klotho-α level compared with control old rats. The levels of Klotho-α, c-fos and brain-derived neurotrophic factors were decreased in the low-calorie high-protein group in Klotho inhibitor's presence compared with the low-calorie high-protein group.

Conclusion: According to our findings, Klotho-α level was reduced in old rats. Low-calorie, high-protein and particularly low-calorie high-protein diets increased this protein level and consequently increased neuronal plasticity and improved memory function.

Graphic Abstract:
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12986-020-00508-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559193PMC
October 2020

The Impact of Sex Differences on Renal Protective Effects of Lipopolysaccharide Preconditioning in Septic Shock.

Iran J Med Sci 2020 Sep;45(5):383-390

Department of Physiology, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran.

Background: Induction of septic shock by lipopolysaccharide (LPS) may lead to acute renal failure. The present study aimed to investigate the impact of sex differences on the effectiveness of low-dose LPS preconditioning (LPS-PC) on LPS-induced acute renal failure in rats.

Methods: This study was conducted at Tehran University of Medical Sciences, in 2017. A total of 48 Wistar rats were equally divided into two groups of male and female rats. The rats in each group were then allocated to three groups (n=8 per group), namely control, septic shock, and LPS-PC group. A high dose of LPS was administered for septic shock induction. LPS-PC was induced by injecting LPS before sepsis induction. The effect of sex differences on renal functional indices, renal oxidative stress markers, plasma tumor necrosis factor-α level, and renal histological changes was evaluated. Data were analyzed using two-way ANOVA followed by Tukey's test.

Results: In the septic shock groups, renal functional parameters (creatinine [Cr] and blood urea nitrogen [BUN]) were increased in both sexes. However, the increase was more significant in male rats (male rats: Cr=2.14±0.13, BUN=81±4.15; female rats: Cr=1.64±0.12, BUN=50±2.7). LPS-PC reduced these indices in both sexes (male rats: Cr=1.24±0.03, BUN=57±4.1; female rats: Cr=0.86±0.02, BUN=30.31±2.25). Renal superoxide dismutase (SOD) activity (male rats: 11.54±1.34, female rats: 24.4±2.04) and catalase (CAT) activity (male rats: 15±1.74, female rats: 25.75±1.97) were significantly higher in the female septic group. LPS-PC significantly increased SOD (male rats: 25.7±2.45, female rats: 42.6±3.31) and CAT (male rats: 37.25±2.34, female rats: 59.21±3.29) activities in renal tissue samples in the LPS-PC group in both sexes compared to the septic groups. In the LPS groups, plasma tumor necrosis factor-α (male rats: 375±25.65, female rats: 285.45±25.94) were significantly higher than in the LPS-PC groups (male rats: 250±21.35, female rats: 121±24.14).

Conclusion: Male rats were more susceptible to sepsis-induced renal damage. LPS-PC had protective effects on the LPS-induced renal injury, and these effects were most prominent in female rats.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.30476/ijms.2020.72461.0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519401PMC
September 2020

Adipose-Derived Mesenchymal Stem Cells and Conditioned Medium Attenuate the Memory Retrieval Impairment During Sepsis in Rats.

Mol Neurobiol 2020 Sep 19;57(9):3633-3645. Epub 2020 Jun 19.

Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, 1417613151, Iran.

In this study, we hypothesized that sepsis induction impairs memory retrieval in rats while transplanted mesenchymal stem cells (MSCs) and MSC-conditioned medium (MSC-CM) application are capable of attenuating those complications. MSCs were obtained from adipose tissue of rats and at the second culture passage; MSCs and MSC-CM were collected. Rats were randomly divided into four experimental groups: sham, CLP, MSC, and MSC-CM. Sepsis was induced by cecal ligation and puncture (CLP) model in the CLP, MSC, and MSC-CM groups. The MSC group received 1 × 10 MSCs/rat (i.p., 2 h after CLP surgery); the MSC-CM rats received the conditioned medium (CM) from 1 × 10 MSCs intraperitoneally 2 h after sepsis induction. Novel object recognition test, sepsis score, and blood pressure measurement were performed 24 h after the treatments. The right hippocampus was taken for western blot analysis. CLP rats showed a significantly higher sepsis score and systolic blood pressure. They also had a significant increase in the phosphorylated form of CAMKII-α, cleaved caspase 3 and Bax/Bcl2 ratio, and a reduction in c-fos protein in the hippocampus tissue samples compared with the sham group. MSC transplantation and MSC-CM administration significantly decreased the mean sepsis score and prevented sepsis-induced attenuation of blood pressure compared with the CLP rats. Animals in the MSC and MSC-CM groups showed a better memory retrieval, attenuation in phosphorylated form of CAMKII-α, cleaved caspase 3 and Bax/Bcl ratio, and an increase in c-fos protein expression compared with the CLP group. It seems that CAMKII and c-fos are inversely involved in regulating memory processes in hippocampus. Phosphorylated form of CaMKII-α overexpression may impair the ability of object recognition. Our findings confirmed that MSC-CM application has more advantages compared with transplanted MSCs and may be offered as a promising therapy for inflammatory diseases such as severe sepsis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12035-020-01991-6DOI Listing
September 2020

Long-term NaHS administration reduces oxidative stress and apoptosis in a rat model of left-side varicocele.

Andrologia 2020 Mar 3;52(2):e13496. Epub 2019 Dec 3.

Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

The main aim of this study was to assay the testicular H S levels in the varicocele rat model and then to investigate the protective effects of NaHS on morphometric changes, sperm parameters, oxidative stress and apoptosis markers in rat's testis. D,L-propargylglycine (PAG) was administrated to show the effects of cystathionine γ-lyase enzyme (CSE) inhibition in the varicocele. Rats were assigned to four groups: (a) Sham, (b) varicocele, (c) varicocele + PAG and (d) varicocele + NaHS. Animals in varicocele + NaHS group received 30 µmol/L NaHS in drinking water for 56 days. In the varicocele + PAG group, animals received PAG 19 mg/kg twice a week. Morphometric assessment, oxidative stress markers, testicular H S levels, sperm parameters, TUNEL assay and expression of Bax/Bcl2 were evaluated at the end of experiment. Testicular H S levels were significantly decreased in varicocele group. NaHS significantly improved sperm parameters, morphometric characteristics and oxidative stress compared to varicocele group. Oxidative stress status deteriorated in the PAG group compared to the varicocele group. This study showed that a low testicular H S level might play a critical role in male infertility. Thus, NaHS administration may be a promising treatment strategy for male infertility in varicocele. In addition, CSE may not be the only important enzyme in testicular H S production.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/and.13496DOI Listing
March 2020

Algorithm for Reliable Detection of Pulse Onsets in Cerebral Blood Flow Velocity Signals.

Front Neurol 2019 11;10:1072. Epub 2019 Oct 11.

Neural Analytics, Inc., Los Angeles, CA, United States.

Transcranial Doppler (TCD) ultrasound has been demonstrated to be a valuable tool for assessing cerebral hemodynamics via measurement of cerebral blood flow velocity (CBFV), with a number of established clinical indications. However, CBFV waveform analysis depends on reliable pulse onset detection, an inherently difficult task for CBFV signals acquired via TCD. We study the application of a new algorithm for CBFV pulse segmentation, which locates pulse onsets in a sequential manner using a moving difference filter and adaptive thresholding. The test data set used in this study consists of 92,012 annotated CBFV pulses, whose quality is representative of real world data. On this test set, the algorithm achieves a true positive rate of 99.998% (2 false negatives), positive predictive value of 99.998% (2 false positives), and mean temporal offset error of 6.10 ± 4.75 ms. We do note that in this context, the way in which true positives, false positives, and false negatives are defined caries some nuance, so care should be taken when drawing comparisons to other algorithms. Additionally, we find that 97.8% and 99.5% of onsets are detected within 10 and 30 ms, respectively, of the true onsets. The algorithm's performance in spite of the large degree of variation in signal quality and waveform morphology present in the test data suggests that it may serve as a valuable tool for the accurate and reliable identification of CBFV pulse onsets in neurocritical care settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2019.01072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6798080PMC
October 2019

Additional effects of erythropoietin pretreatment, ischemic preconditioning, and N-acetylcysteine posttreatment in rat kidney reperfusion injury

Turk J Med Sci 2019 08 8;49(4):1249-1255. Epub 2019 Aug 8.

Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Background/aim: Since the nature of ischemia/reperfusion (IR)-induced tissue damage is multifactorial and complex, in the current study, the effects of multiple treatment strategies via concomitant administration of erythropoietin (EPO) and N-acetylcysteine (NAC) with an ischemic preconditioning (IPC) regimen on renal IR injury were examined.

Materials And Methods: Thirty male Wistar rats were subjected to bilateral occlusion of the renal pedicles for 50 min followed by reperfusion. EPO (1000 IU/kg) was administered for 3 days, as well as IPC before the IR and NAC (150 mg/kg) administration for 4 days after IR. The animals were randomly allocated into 6 groups (n = 5): sham, IR, EPO+IR, IPC+IR, NAC+IR, and EPO+IPC+NAC+IR. Kidney tissues and blood samples were obtained for oxidative stress, proinflammatory cytokines, and renal functional evaluations.

Results: IR caused significant inflammatory response, oxidative stress, and reduced renal function. Treatment with EPO, IPC, and NAC or a combination of two of them attenuated renal dysfunction and reduced the oxidative stress and inflammatory markers. Rats treated with the combination of EPO, IPC, and NAC showed a higher degree of protection compared to the other groups.

Conclusion: These results showed that concomitant administration of EPO and IPC along with posttreatment NAC may have additive beneficial effects on kidney IR injury during IR-induced acute renal failure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3906/sag-1812-228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018199PMC
August 2019

Objective Assessment of Beat Quality in Transcranial Doppler Measurement of Blood Flow Velocity in Cerebral Arteries.

IEEE Trans Biomed Eng 2020 03 17;67(3):883-892. Epub 2019 Jun 17.

Objective: Transcranial Doppler (TCD) ultrasonography measures pulsatile cerebral blood flow velocity in the arteries and veins of the head and neck. Similar to other real-time measurement modalities, especially in healthcare, the identification of high-quality signals is essential for clinical interpretation. Our goal is to identify poor quality beats and remove them prior to further analysis of the TCD signal.

Methods: We selected objective features for this purpose including Euclidean distance between individual and average beat waveforms, cross-correlation between individual and average beat waveforms, ratio of the high-frequency power to the total beat power, beat length, and variance of the diastolic portion of the beat waveform. We developed an iterative outlier detection algorithm to identify and remove the beats that are different from others in a recording. Finally, we tested the algorithm on a dataset consisting of more than 15 h of TCD data recorded from 48 stroke and 34 in-hospital control subjects.

Results: We assessed the performance of the algorithm in the improvement of estimation of clinically important TCD parameters by comparing them to that of manual beat annotation. The results show that there is a strong correlation between the two, that demonstrates the algorithm has successfully recovered the clinically important features. We obtained significant improvement in estimating the TCD parameters using the algorithm accepted beats compared to using all beats.

Significance: Our algorithm provides a valuable tool to clinicians for automated detection of the reliable portion of the data. Moreover, it can be used as a pre-processing tool to improve the data quality for automated diagnosis of pathologic beat waveforms using machine learning.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TBME.2019.2923146DOI Listing
March 2020

Velocity Curvature Index: a Novel Diagnostic Biomarker for Large Vessel Occlusion.

Transl Stroke Res 2019 10 6;10(5):475-484. Epub 2018 Oct 6.

Neural Analytics, Inc., 2440 S. Sepulveda Blvd. Suite 115, Los Angeles, CA, 90064, USA.

Despite being a conveniently portable technology for stroke assessment, Transcranial Doppler ultrasound (TCD) remains widely underutilized due to complex training requirements necessary to reliably obtain and interpret cerebral blood flow velocity (CBFV) waveforms. The validation of objective TCD metrics for large vessel occlusion (LVO) represents a first critical step toward enabling use by less formally trained personnel. In this work, we assess the diagnostic utility, relative to current standard CT angiography (CTA), of a novel TCD-derived biomarker for detecting LVO. Patients admitted to the hospital with stroke symptoms underwent TCD screening and were grouped into LVO and control groups based on the presence of CTA confirmed occlusion. Velocity curvature index (VCI) was computed from CBFV waveforms recorded at multiple depths from the middle cerebral arteries (MCA) of both cerebral hemispheres. VCI was assessed for 66 patients, 33 of which had occlusions of the MCA or internal carotid artery. Our results show that VCI was more informative when measured from the cerebral hemisphere ipsilateral to the site of occlusion relative to contralateral. Moreover, given any pair of bilateral recordings, VCI separated LVO patients from controls with average area under receiver operating characteristic curve of 92%, which improved to greater than 94% when pairs were selected by maximal velocity. We conclude that VCI is an analytically valid candidate biomarker for LVO diagnosis, possessing comparable accuracy, and several important advantages, relative to current TCD diagnostic methodologies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12975-018-0667-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733810PMC
October 2019

A Cross-Sectional Study on Cerebral Hemodynamics After Mild Traumatic Brain Injury in a Pediatric Population.

Front Neurol 2018 5;9:200. Epub 2018 Apr 5.

Neural Analytics, Inc., Los Angeles, CA, United States.

The microvasculature is prominently affected by traumatic brain injury (TBI), including mild TBI (concussion). Assessment of cerebral hemodynamics shows promise as biomarkers of TBI, and may help inform development of therapies aimed at promoting neurologic recovery. The objective of this study was to assess the evolution in cerebral hemodynamics observable with transcranial Doppler (TCD) ultrasound in subjects suffering from a concussion at different intervals during recovery. Pediatric subjects between the ages of 14 and 19 years clinically diagnosed with a concussion were observed at different points post-injury. Blood flow velocity in the middle cerebral artery was measured with TCD. After a baseline period, subjects participated in four breath holding challenges. Pulsatility index (PI), resistivity index (RI), the ratio of the first two pulse peaks (P2R), and the mean velocity (MV) were computed from the baseline section. The breath hold index (BHI) was computed from the challenge sections. TCD detected two phases of hemodynamic changes after concussion. Within the first 48 h, PI, RI, and P2R show a significant difference from the controls ( = -3.10;  < 0.01,  = -2.86;  < 0.01, and  = 2.62;  < 0.01, respectively). In addition, PI and P2R were not correlated ( = -0.36;  = 0.23). After 48 h, differences in pulsatile features were no longer observable. However, BHI was significantly increased when grouped as 2-3, 4-5, and 6-7 days post-injury ( = 2.72;  < 0.01,  = 2.46;  = 0.014, and  = 2.38;  = 0.018, respectively). To our knowledge, this is the first longitudinal study of concussions using TCD. In addition, these results are the first to suggest the multiple hemodynamic changes after a concussion are observable with TCD and could ultimately lead to a better understanding of the underlying pathophysiology. In addition, the different hemodynamic responses to a concussion as compared to severe traumatic brain injuries highlight the need for specific diagnostic and therapeutic treatments of mild head injuries in adolescents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2018.00200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5895751PMC
April 2018

Long-term exercise restores hydrogen sulfide in the kidney and contributes to exercise benefits in 5/6 nephrectomized rats.

Clin Exp Hypertens 2019 9;41(1):87-91. Epub 2018 Mar 9.

a Department of Physiology, Faculty of Medicine , Tehran University of Medical Sciences , Tehran , Iran.

Physical exercise is shown to have protective effects on chronic kidney disease (CKD). CKD itself is associated with a reduction in renal hydrogen sulfide (H2S) concentration. This study was designed to investigate whether protective effects of exercise in 5/6 nephrectomized (5/6 NX) rats is associated with H2S levels in the kidney? Twenty four male Wistar rats weighing 250-300 g were assigned into 4 groups: 1- Sham 2- Sham exercise 3-5/6 NX 4-5/6 NX+exercise. To induce CKD, 4 days after removing upper and lower one-third parts of the left kidney, total right nephrectomy was performed. In the Sham groups, anesthesia and surgery were performed like the other groups without removal of the kidney mass. Exercise was performed by treadmill at a speed of 18 m/min for 8 weeks. At the end of the twelfth week, blood and kidney samples were collected to measure renal function (levels of plasma urea and creatinine), oxidative stress markers (renal MDA level and SOD activity), and histological indices. Eight weeks exercise significantly improved serum creatinine, BUN, renal MDA level, SOD activity, renal sympathetic nerve activity (RSNA), hypertension, and renal histology in addition to renal H2S level compared to the 5/6 NX group. The results suggest that regular exercise improves renal oxidative status and ameliorates renal damage, hypertension, and RSNA in 5/6 nephrectomized rats. These improvements by exercise might be associated with the increase in renal H2S level.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10641963.2018.1445752DOI Listing
January 2019

Resuscitative therapy with erythropoietin reduces oxidative stress and inflammatory responses of vital organs in a rat severe fixed-volume hemorrhagic shock model.

Gen Physiol Biophys 2018 Jan;37(1):83-92

Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Hemorrhagic shock (HS) still has a high mortality rate and none of the known resuscitative regimens completely reverse its adverse outcomes. This study investigated the effects of different models of resuscitative therapy on the healing of organ damage in a HS model. Male Wistar rats were randomized into six groups: Sham, without HS induction; HS, without resuscitation; HS+Blood, resuscitation with the shed blood; HS+Blood+NS, resuscitation with blood and normal saline; HS+Blood+RL, resuscitation with blood and Ringer's lactate; EPO, erythropoietin was added to the blood and RL. Blood and urine samples were obtained 3 h after resuscitation. Kidney, liver and brain tissue samples were harvested for multiple organ failure evaluation. Survival rate was the highest in the Sham, EPO and HS+Blood+RL groups compared to others. Plasma creatinine concentration, ALT, AST, urinary NAG activity and renal NGAL mRNA expression significantly increased in the HS+Blood+RL group compared to the Sham group. There was a significant increase in tissue oxidative stress markers and pro-inflammatory cytokines in HS+Blood+RL group compared to the Sham rats. EPO had more protective effects on multiple organ failure compared to the HS+Blood+RL group. EPO, as a resuscitative treatment, attenuated HS-induced organ damage. It seems that it has a potential to be attractive for clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/124149/gpb_2017019DOI Listing
January 2018

Protective effects of hydrogen sulfide on chronic kidney disease by reducing oxidative stress, inflammation and apoptosis.

EXCLI J 2018 2;17:14-23. Epub 2018 Jan 2.

Department of Physiology, Faculty of Medicine, Hamedan University of Medical Sciences, Hamedan, Iran.

The current study aimed to examine the renoprotective effects of long-term treatment with sodium hydrosulfide (NaHS), a prominent hydrogen sulfide donor, in 5/6 nephrectomy animal model. Twenty-four rats were randomly divided into 3 groups including sham-operated group (Sham), 5/6-nephrectomized group (5/6 Nx), and NaHS-treated group (5/6Nx+NaHS). NaHS (30 micromol/l) was added twice daily into the drinking water and renal failure was induced by 5/6 nephrectomy. Twelve weeks after surgical procedure, blood pressure, creatinine clearance (CCr), urine concentration of neutrophil gelatinase associated lipocalin (NGAL) and tissue concentration of malondialdehyde (MDA), superoxide dismutase (SOD), as well as renal morphological changes, apoptosis (cleaved caspase-3) and inflammation (p-NF-κB) were measured. Five-sixth nephrectomy induced severe renal damage as indicated by renal dysfunction, hypertension and significant histopathological injury which were associated with increased NGAL and MDA levels, oxidant/antioxidant imbalance, decreased SOD activity and CCr and also overexpression of p-NF-κB and cleaved caspase-3 proteins. Instead, NaHS treatment attenuated renal dysfunction through reduction of NGAL concentration, hypertension, CCr, oxidant/antioxidant imbalance, inflammation and apoptosis. These findings suggest that long term NaHS treatment can be useful in preventing the progression of CKD by improving oxidant/antioxidant balance and reducing inflammation and apoptosis in the kidney.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.17179/excli2017-711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5780625PMC
January 2018

Nephroprotection through the Akt/eNOS pathway by centrally administered erythropoietin in a rat model of fixed-volume hemorrhage.

Life Sci 2018 Jan 6;193:180-185. Epub 2017 Nov 6.

Department of Biostatistics, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.

Aims: This study was designed to investigate the protective effects of centrally administered erythropoietin (EPO) on brain oxidative stress and inflammatory markers to protect the kidneys during hemorrhagic shock (HS).

Main Methods: Animals were assigned into three groups (n=6). Sham rats were subjected to cannulation of femoral artery and vein as well as stereotaxic surgery. In HS group, 50% of total blood volume was withdrawn and resuscitation was started 2h later. In EPO group, stereotaxic surgery in lateral ventricle was performed one week before induction of HS for administration of EPO (2IU) just before resuscitation. Plasma samples, kidney and brain tissues were allocated after a further 3h in all animals.

Key Findings: There was a significant increase in survival rate in the EPO group (69.3%) compared to the HS group (35.7%). Brain EPO administration significantly attenuated the rises in BUN, plasma Cr and NGAL, brain and renal MDA content and also increased SOD activity in the kidney and brain compared to the HS group. Brain, plasma and kidney TNF-α and IL-6 levels were significantly reduced by EPO compared to HS group. EPO increased the phosphorylation of Akt on Ser473 and eNOS mRNA expression in the kidney tissue compared to the HS group.

Significance: In conclusion, centrally administered EPO reduced pro-inflammatory and oxidative stress indices in the kidney and reduced apoptosis by activation of the Akt/eNOS signaling pathway. Hence, it can be hypothesized that EPO may play a major role in the central regulation of renal system as a neuromodulator.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lfs.2017.11.003DOI Listing
January 2018

Transient Inactivation of Shell Part of Nucleus Accumbens Inhibits and Exacerbates Stress-Induced Metabolic Alterations in Wistar Rats.

Basic Clin Neurosci 2017 Mar-Apr;8(2):121-128

Department of Biology, Faculty of Science, Campus of Shahid Bahonar, Farhangiaan University, Hamadan, Iran.

Introduction: The role of different parts of the extended amygdala in metabolic signs of stress is not well understood. In the present study, we decided to evaluate the impact of the shell part of nucleus accumbens (NAc) on metabolic disturbance induced by electro foot shock stress using transient inactivation method in the rat.

Methods: Male Wistar rats (W: 230-250 g) were canuulated unilaterally in the shell part of nucleus accumbens and left one week for recovery. Five minutes before each stress session, the animals either received sterile saline (0.25 μl/side) (control) or lidocaine 2% (0.25 μl/side) (experiment). Blood samples were taken from rats' retro-orbital sinus for plasma corticosterone measurements. In addition, animals' weight gain, food and water intake, locomotor activity, and rearing were recorded.

Results: Stress reduced weight gain and food intake, increased water intake and plasma corticosterone level, and reduces locomotor activity and rearing. Transient inactivation of the right side of the NAc inhibits the stress effect on weight gain, water intake and plasma corticosterone level, but not food intake. However, when the left side of the NAc was inactivated, only weight gain was affected and other parameters were not differing from stress group. Even thought, the plasma corticosterone level was elevated.

Conclusion: In conclusion, our data indicated that right side of shell part of NAc transient inactivation leads to reduction in metabolic signs of stress but left side of shell part of the NAc inactivation even exacerbates stress signs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18869/nirp.bcn.8.2.121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440921PMC
May 2017

Renal tissue pro-inflammatory gene expression is reduced by erythropoietin in rats subjected to hemorrhagic shock.

J Nephropathol 2017 Mar 29;6(2):69-73. Epub 2016 Nov 29.

Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Background: Hemorrhagic shock (HS) is a condition produced by considerable loss of intravascular volume, which may eventually lead to organ damage and death.

Objectives: In the present study, the potential implication of the kidney tissue tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) were evaluated in the protective effects of erythropoietin (EPO) during HS.

Materials And Methods: Male Wistar rats were randomized into three experimental groups; Sham, HS (hemorrhagic shock and resuscitation), and EPO (erythropoietin). HS was induced by 50% blood volume hemorrhage over 30 minutes. After 2 hours, resuscitation was performed within 30 minutes. In the EPO group, EPO (300 IU/kg, i.v.) was administered 10 minutes before HS induction. Urine was collected to determine urinary N-acetyl-β-D-glucosaminidase (NAG) activity level. The kidney cytokines (TNF-α, IL-6 and IL-10) mRNA expressions were measured by real-time polymerase chain reaction (PCR).

Results: HS rats showed significant increase in urinary NAG activity compared to the sham group. EPO significantly attenuated the rises in urinary NAG activity compared to the HS group. In the HS animals, renal TNF-α and IL-6 mRNA expressions increased whereas no difference was observed in IL-10 mRNA expression between the HS and sham groups. EPO was able to decrease renal TNF-α and IL-6 production and increase IL-10 mRNA expression.

Conclusions: In this study, we demonstrated that EPO attenuates kidney damage in rats subjected to HS. The beneficial effects of EPO may be at least partly mediated by modifications in the inflammatory cascade.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15171/jnp.2017.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5418073PMC
March 2017

Up-regulation of nitric oxide synthases by erythropoietin alone or in conjunction with ischemic preconditioning in ischemia reperfusion injury of rat kidneys.

Gen Physiol Biophys 2017 Jul 4;36(3):281-288. Epub 2017 May 4.

Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, International campus, Tehran, Iran.

The effects of erythropoietin (EPO) alone or in conjunction with ischemic preconditioning (IPC) on nitric oxide synthase as well as comparing their effects on oxidative stress and proinflammatory cytokines are studied. Rats underwent bilateral renal ischemia of 50 min followed by 24 h reperfusion. They were administered EPO (5000 iu/kg i.p.) and/or subjected to IPC and sacrificed after 24 h, then plasma and tissue samples were obtained. Treatment of either EPO or IPC and their combination attenuates oxidative stress, decreases histological damages, inhibits proinflammatory response, and up-regulates iNOS and eNOS gene expression compared to IR group. In addition, EPO+IPC and EPO treatment produced significant up-regulation in iNOS gene expression compared to IPC group. In IPC and EPO+IPC groups, more powerful effect on up-regulation of eNOS gene expression was shown compared to EPO group. Our findings suggest that treatment with EPO or IPC and their combination improve renal function and preserve tubular damage induced by IR injury. These advantageous effects were closely related to reducing oxidative stress, suppressing proinflammatory response and enhancing generation of NO. IPC was more powerful in enhancement of eNOS gene expression compared to EPO that was more effective in increasing of iNOS gene expression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4149/gpb_2016058DOI Listing
July 2017

Papaver Rhoeas L. Hydroalcoholic Extract Exacerbates Forced Swimming Test-Induced Depression in Mice.

Basic Clin Neurosci 2016 Jul;7(3):195-202

Neuroscience Research Center, Baqiyatallah (a.s.) University of Medical Sciences, Tehran, Iran.

Introduction: Depression is one of the most frequent psychiatric disorders in the world with occurs with higher incidence in women. In the present study, the effect of water-alcoholic extract of Papaver rhoeas L. on forced swimming test (FST) in Swiss-Webster mice were examined.

Methods: We used Swiss-Webster mice (20-25 g) to execute FST on them. The plant extract (1, 10, 30, and 100 mg/kg) was injected to the animals 30 minutes before each session. Fluoxetine (20 mg/kg) was used as standard antidepressant drug. In another group of animals, 30 minutes after extract administration, blood samples were taken from retro-orbital sinus for corticosterone assay. Yet in third group, the drugs were injected to the animals and 30 minutes later, their activities were tested in an open field apparatus.

Results: Our experiments showed that the extract efficiently reduced FST time both in male and female mice dose-dependently. This effect was comparable with fluoxetine. In addition, corticosterone assay indicated that plasma corticosterone in animals which received extract was higher than those amounts in fluoxetine and saline controls. Moreover, the animals did not show any motor activity deficit in all doses of the extract and fluoxetine compared to saline control.

Conclusion: The extract of Papaver rhoeas can reduce immobility time which is comparable to the effect of fluoxetine. Also the effect of the extract is contrary to its effects on plasma corticosterone level and or animals' activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15412/J.BCN.03070304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981831PMC
July 2016

Vestibular Compensation in Unilateral Patients Often Causes Both Gain and Time Constant Asymmetries in the VOR.

Front Comput Neurosci 2016 29;10:26. Epub 2016 Mar 29.

Department of Biomedical Engineering, McGill University Montreal, QC, Canada.

The vestibulo-ocular reflex (VOR) is essential in our daily life to stabilize retinal images during head movements. Balanced vestibular functionality secures optimal reflex performance which otherwise can be distorted by peripheral vestibular lesions. Luckily, vestibular compensation in different neuronal sites restores VOR function to some extent over time. Studying vestibular compensation gives insight into the possible mechanisms for plasticity in the brain. In this work, novel experimental analysis tools are employed to reevaluate the VOR characteristics following unilateral vestibular lesions and compensation. Our results suggest that following vestibular lesions, asymmetric performance of the VOR is not only limited to its gain. Vestibular compensation also causes asymmetric dynamics, i.e., different time constants for the VOR during leftward or rightward passive head rotation. Potential mechanisms for these experimental observations are provided using simulation studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fncom.2016.00026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4809898PMC
April 2016

Ameliorative Effect of Recombinant Human Erythropoietin and Ischemic Preconditioning on Renal Ischemia Reperfusion Injury in Rats.

Nephrourol Mon 2015 Nov 29;7(6):e31152. Epub 2015 Nov 29.

Department of Physiology, Faculty of Medicine, Hamedan University of Medical Sciences, Hamedan, IR Iran.

Background: Ischemia-reperfusion (IR) injury is one of the most common causes of renal dysfunction. There is increasing evidence about the role of the reactive oxygen species (ROS) in these injuries and endogenous antioxidants seem to have an important role in decreasing the renal tissue injury.

Objectives: The aim of this study was to compare the effect of recombinant human erythropoietin (EPO) and ischemic preconditioning (IPC) on renal IR injury.

Materials And Methods: Twenty four male Wistar rats were allocated into four experimental groups: sham-operated, IR, EPO + IR, and IPC + IR. Rats were underwent 50 minutes bilateral ischemia followed by 24 hours reperfusion. Erythropoietin (5000 IU/kg, i.p) was administered 30 minutes before onset of ischemia. Ischemic preconditioning was performed by three cycles of 3 minutes ischemia followed by 3 minutes reperfusion. Plasma concentrations of urea and creatinine were measured. Kidney samples were taken for reactive oxidative species (ROS) measurement including superoxide dismutase (SOD) activity, glutathione (GSH) contents, and malondialdehyde (MDA) levels.

Results: Compared to the sham group, IR led to renal dysfunction as evidenced by significantly higher plasma urea and creatinine. Treatment with EPO or IPC decreased urea, creatinine, and renal MDA levels and increased SOD activity and GSH contents in the kidney.

Conclusions: Pretreatment with EPO and application of IPC significantly ameliorated the renal injury induced by bilateral renal IR. However, both treatments attenuated renal dysfunction and oxidative stress in kidney tissues. There were no significant differences between pretreatment with EPO or application of IPC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5812/numonthly.31152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4744640PMC
November 2015

Automatic Classification of the Vestibulo-Ocular Reflex Nystagmus: Integration of Data Clustering and System Identification.

IEEE Trans Biomed Eng 2016 Apr 7;63(4):850-8. Epub 2015 Sep 7.

The vestibulo-ocular reflex (VOR) plays an important role in our daily activities by enabling us to fixate on objects during head movements. Modeling and identification of the VOR improves our insight into the system behavior and improves diagnosis of various disorders. However, the switching nature of eye movements (nystagmus), including the VOR, makes dynamic analysis challenging. The first step in such analysis is to segment data into its subsystem responses (here slow and fast segment intervals). Misclassification of segments results in biased analysis of the system of interest. Here, we develop a novel three-step algorithm to classify the VOR data into slow and fast intervals automatically. The proposed algorithm is initialized using a K-means clustering method. The initial classification is then refined using system identification approaches and prediction error statistics. The performance of the algorithm is evaluated on simulated and experimental data. It is shown that the new algorithm performance is much improved over the previous methods, in terms of higher specificity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TBME.2015.2477038DOI Listing
April 2016

Hybrid model of the context dependent vestibulo-ocular reflex: implications for vergence-version interactions.

Front Comput Neurosci 2015 9;9. Epub 2015 Feb 9.

Department of Biomedical Engineering, McGill University Montreal, QC, Canada.

The vestibulo-ocular reflex (VOR) is an involuntary eye movement evoked by head movements. It is also influenced by viewing distance. This paper presents a hybrid nonlinear bilateral model for the horizontal angular vestibulo-ocular reflex (AVOR) in the dark. The model is based on known interconnections between saccadic burst circuits in the brainstem and ocular premotor areas in the vestibular nuclei during fast and slow phase intervals of nystagmus. We implemented a viable switching strategy for the timing of nystagmus events to allow emulation of real nystagmus data. The performance of the hybrid model is evaluated with simulations, and results are consistent with experimental observations. The hybrid model replicates realistic AVOR nystagmus patterns during sinusoidal or step head rotations in the dark and during interactions with vergence, e.g., fixation distance. By simply assigning proper nonlinear neural computations at the premotor level, the model replicates all reported experimental observations. This work sheds light on potential underlying neural mechanisms driving the context dependent AVOR and explains contradictory results in the literature. Moreover, context-dependent behaviors in more complex motor systems could also rely on local nonlinear neural computations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fncom.2015.00006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4321407PMC
February 2015

Identification of the vestibulo-ocular reflex dynamics.

Annu Int Conf IEEE Eng Med Biol Soc 2014 ;2014:1485-8

The vestibulo-ocular reflex (VOR) plays an important role in our daily activities by enabling us to fixate on objects during head movements. Modeling and identification of the VOR improves our insight into the system behavior and helps in diagnosing various disorders. However, the switching nature of eye movements, including the VOR, makes the dynamic analysis challenging. In this work we are using integration of subspace and prediction error methods to analyze VOR dynamics. The performance of the method is evaluated using simulation studies and experimental data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/EMBC.2014.6943882DOI Listing
June 2016

New view on treatment of drug dependence.

Basic Clin Neurosci 2014 ;5(1):96-7

Neuroscience Research Center, Baqiyatallah (a.s.) University of Medical Sciences, Tehran, Iran.

In the 1960s, discovery of pleasure system (defined as reward system) in the brain that may underlie drug reward and addiction encouraged many scientists to investigate the mechanisms by which drug abuse affects central nervous system function. In this regard, investigators developed several drugs targeting the brain reward system for drug dependence therapy. However, no positive results obtained in drug addiction treatment. It seems that more brain systems other than brain reward system must be considered in this regard.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4202597PMC
December 2014

Inhibitory effect of NMDA receptors in the ventral tegmental area on hormonal and eating behavior responses to stress in rats.

Behav Neurol 2014 7;2014:294149. Epub 2014 Aug 7.

Department of Physiology and Biophysics, Faculty of Medicine, Baqiyatallah (a.s.) University of Medical Sciences, Tehran 19395-6558, Iran.

Background: Stress and its consequences are among the causes of accidents.

Objective: The effects of intraventral tegmental area (I-VTA) memantine on the plasma corticosterone and eating parameters disturbance induced by acute stress were investigated.

Methods: Male Wistar rats (W: 250-300 g) were divided into control and experiential groups, each of which received memantine either intra-VTA or peripherally. One week after bilateral cannulation, the rats received memantine (1 and 5 μg/Rat) five min before electroshock stress. The other experimental groups received memantine (1 and 5 mg/kg) intraperitoneally 30 min before stress. The control groups received saline or memantine but did not experience stress. Food and water intake and plasma corticosterone level were recorded.

Results: Results showed that stress decreases food intake but does not change water intake and increase in plasma corticosterone level. Intraperitoneal memantine administration slightly inhibits the stress effects on food intake. However, water intake and plasma corticosterone level were increased. Intra-VTA memantine reduces the effects of stress on corticosterone and water intake.

Conclusion: It could be concluded that inhibition of glutamate NMDA receptors in the VTA by memantine leads to the inhibition of the eating behavior parameters and plasma corticosterone level disturbance induced by stress in rats.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2014/294149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143587PMC
April 2016

Angiotensin II in paraventricular nucleus contributes to sympathoexcitation in renal ischemia-reperfusion injury by AT1 receptor and oxidative stress.

J Surg Res 2015 Jan 5;193(1):361-7. Epub 2014 Jul 5.

Research Department, EqlimDanesh Co. Ltd, Tehran, Iran.

Background: To investigate the effect of angiotensin II (Ang II) in the hypothalamic paraventricular nucleus (PVN) on renal ischemia-reperfusion (IR) injury and to assay the role of renal sympathetic nerve activity (RSNA).

Methods: A cannula was inserted into the right side PVN in Sprague-Dawley rats for microinjection of Ang II (3, 30, and 300 ng); Ang II AT1 receptor antagonist, losartan (0.3 μg); and the superoxide dismutase (SOD) mimetic, tempol (20 nmol) before right side nephrectomy. After 1 wk, renal IR injury was induced by clamping the left renal artery for 45 min, and then reperfusion for 3 or 24 h. The extent of renal damage was determined by evaluation of renal functional indices. RSNA was recorded in all groups. Oxidative stress indices (SOD activity and malondialdehyde levels) were assayed in the PVN.

Results: Microinjection of pharmacologic doses of Ang II into the PVN exaggerated renal IR injury, increased RSNA and oxidative stress in the PVN dose dependently. The effects of Ang II (3 ng) was prevented by pretreatment with losartan into the PVN. Furthermore, the deleterious effects of Ang II on renal IR injury, RSNA, and oxidative stress were abolished by pretreatment with tempol.

Conclusions: These results indicate that the PVN is a responsive site for central Ang II increment damage in renal ischemia-reperfusion injury. We suggested the central effects of Ang II in the PVN on renal IR injury are mediated by AT1 receptors and oxidative stress in the PVN, and the peripheral effects by a sympathetic pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jss.2014.06.042DOI Listing
January 2015
-->