Publications by authors named "Mohammad Reza Raoufy"

38 Publications

Clinical Features and Outcomes of ICU Patients with COVID-19 Infection in Tehran, Iran: a Single-Centered Retrospective Cohort Study.

Tanaffos 2020 Dec;19(4):300-311

Clinical Tuberculosis and Epidemiology Research Center, NRITLD, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: The clinical characteristics of the novel coronavirus disease (COVID-19) were diverse and unspecific. Here, we identified the associated factors with surviving of COVID-19 ICU patients based on the clinical characteristics of patients admitted to one of the Corona Centre Hospitals of Iran.

Materials And Methods: This cohort study was performed retrospectively from February to June 2020 on 133 COVID-19 patients admitted to 4 intensive care units of Masih Daneshvari Hospital in Tehran, Iran. Demographic, medical, clinical manifestation at admission, laboratory parameters and outcome data were obtained from medical records. Also the SOFA and APACHE II scores were calculated. All data were analyzed using SPSS (version 23, IBM Corp.) software.

Results: The median (IQR) age of the patients was 62.0 (54.0-72.0) years in total. RT-PCR of throat swab SARS-CoV-2 in 80 patients (60.2%) was positive. Total mortality rate was 57.9 percent (77 patients). Dyspnea, hypertension and chronic pulmonary diseases were significantly common in non-survivors than survivors (p<0.05). Both SOFA and APACHE II scores were significantly higher in the non-survivors (p<0.05). Also other significant differences were observed in other parameters of the study.

Conclusion: The mortality rate of COVID-19 patients admitted to ICU is generally high. Dyspnea as initial presentation and comorbidity, especially hypertension and pulmonary diseases, may be associated with higher risk of severe disease and consequent mortality rate. Also, higher SOFA and APACHE II scores could indicate higher mortality in patients admitted to ICU.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088143PMC
December 2020

Allergic rhinitis impairs working memory in association with drop of hippocampal - Prefrontal coupling.

Brain Res 2021 May 11;1758:147368. Epub 2021 Feb 11.

Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; Institute for Brain Sciences and Cognition, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address:

Allergic rhinitis (AR) is a chronic inflammatory disease frequently associated with a deficit in learning and memory. Working memory is an important system for decision making and guidance, which depends on interactions between the ventral hippocampus (vHipp) and the prelimbic prefrontal cortex (plPFC). It is still unclear whether AR influences the activity and coupling of these brain areas, which consequently may impair working memory. The current study aimed to examine alterations of the vHipp-plPFC circuit in a rat model of AR. Our results show decreased working memory performance in AR animals, accompanied by a reduction of theta and gamma oscillations in plPFC. Also, AR reduces coherence between vHipp and plPFC in both theta and gamma frequency bands. Cross-frequency coupling analyses confirmed a reduced interaction between hippocampal theta and plPFC gamma oscillations. Granger causality analysis revealed a reduction in the causal effects of vHipp activity on plPFC oscillations and vice versa. A significant correlation was found between working memory performance with disruption of functional connectivity in AR animals. In summary, our data show that in AR, there is a deficit of functional coupling between hippocampal and prefrontal network, and suggest that this mechanism might contribute to working memory impairment in individuals with AR.
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http://dx.doi.org/10.1016/j.brainres.2021.147368DOI Listing
May 2021

Rhythmic air-puff into nasal cavity modulates activity across multiple brain areas: A non-invasive brain stimulation method to reduce ventilator-induced memory impairment.

Respir Physiol Neurobiol 2021 05 28;287:103627. Epub 2021 Jan 28.

Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; Institute for Brain Sciences and Cognition, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address:

Mechanical ventilation (MV) can result in long-term brain impairments that are resistant to treatment. The mechanisms underlying MV-induced brain function impairment remain unclear. Since nasal airflow modulates brain activity, here we evaluated whether reinstating airflow during MV could influence the memory performance of rats after recovery. Rats were allocated into two study groups: one group received rhythmic air-puff into the nasal cavity during MV and a control group that underwent ventilation without air-puff. During MV, air-puffs induced time-locked event potentials in OB, mPFC and vHPC and significantly increased the oscillatory activity at the air-puff frequency. Furthermore, in mPFC and vHPC, (but not in OB), delta and theta oscillations were more prominent during air-puff application. After recovery, working memory performance was significantly higher in the air-puff group compared to control. Our study thus suggests a promising non-invasive brain stimulation approach to alleviate the neurological complications of prolonged mechanical ventilation.
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http://dx.doi.org/10.1016/j.resp.2021.103627DOI Listing
May 2021

An optimized animal model of lysolecithin induced demyelination in optic nerve; more feasible, more reproducible, promising for studying the progressive forms of multiple sclerosis.

J Neurosci Methods 2021 Mar 27;352:109088. Epub 2021 Jan 27.

Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box:14115-331, Tehran, Iran; Institute for Brain and Cognition, Tarbiat Modares University, P.O. Box:14115-331, Tehran, Iran; Department of Brain and Cognitive Sciences, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, P.O. Box:14115-331, Tehran, Iran. Electronic address:

Background: Multiple Sclerosis (MS) is a demyelinating disease leading to long-term neurological deficit due to unsuccessful remyelination and axonal loss. Currently, there are no satisfactory treatments for progressive MS somewhat due to the lack of an adequate animal model for studying the mechanisms of disease progression and screening new drugs.

New Method: Lysolecithin (LPC) or agarose-gel loaded LPC (AL-LPC) were applied to mouse optic nerve behind the globe via a minor surgery. Agarose loading was used to achieve longer time of LPC exposure and subsequently long-lasting demyelination.

Results: The lesion sites characterized by luxol fast blue (LFB), FluoroMyelin, Bielschowsky's staining, and immunostaining showed extensive demyelination and axonal damage. The loss of Retinal ganglion cells (RGCs) in the corresponding retinal layer was shown by immunostaining and H&E staining. Visual evoked potential (VEP) recordings showed a significant increase in the latency of the P1 wave and a decrease in the amplitude of the P1N1 wave.

Comparison With Existing Methods: The new approach with a very minor surgery seems to be more feasible and reproducible compared to stereotaxic LPC injection to optic chiasm. Our data revealed prolonged demyelination, axonal degeneration and RGCs loss in both AL-LPC and LPC groups; however, these pathologies were more extensive in the AL-LPC group.

Conclusion: The optimized model provides a longer demyelination time frame and axonal damage followed by RGC degeneration; which is of exceptional interest in investigating axonal degeneration mechanisms and screening the new drugs for progressive MS.
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http://dx.doi.org/10.1016/j.jneumeth.2021.109088DOI Listing
March 2021

Inhibition of Rho-kinase improves response to deep inspiration in ovalbumin-sensitized guinea pigs.

Iran J Basic Med Sci 2020 Dec;23(12):1584-1589

Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Objectives: The modulatory effect of deep inspiration (DI) on airway constriction is impaired in asthma. However, mechanisms underlying this impairment are not clear. Since there is evidence indicating that Rho-kinase activation mediates force maintenance under oscillatory strain, we investigated the impact of Rho-kinase inhibition on the bronchodilatory effect of DI in ovalbumin (OVA) sensitized guinea pigs.

Materials And Methods: forty-eight male Dunkin Hartley guinea pigs were divided into 8 groups including saline/ constant, saline/DI, OVA/constant, OVA/DI, Rho-I/OVA/constant, Rho-I/OVA/DI, OVA-Rho-I/MCh/constant, and OVA-Rho-I/MCh/DI. Animals were subjected to 12 inhalations of OVA or saline aerosol. Guinea pigs in Rho-I/OVA/constant or DI groups were treated with the Rho-kinase inhibitor (Rho-I) (Y-27632, 1 mM aerosols) prior to the last 8 allergen inhalations and OVA-Rho-I/MCh/constant or DI groups received Y-27632 at the end of allergen sensitization protocol before methacholine challenge. The bronchodilatory effect of DI in guinea pigs that were exposed to methacholine was assessed by using an animal ventilator. The bronchodilatory effect was assessed using several parameters: the airway pressure maintenance, airway pressure recovery, and decline of airway pressure.

Results: Results indicated that application of Y-27632 prior to methacholine challenge reduces the airway smooth muscle ability to maintain pressure and also causes further decline in airway pressure in OVA-sensitized animals undergone DI. However, the inhibition of Rho-kinase before OVA inhalations had minimal effect.

Conclusion: We propose that alteration of Rho-kinase signaling pathway may be one of the mechanisms underlying the impairment of DI-induced bronchodilation in OVA-sensitized guinea pigs.
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http://dx.doi.org/10.22038/ijbms.2020.46258.10683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811819PMC
December 2020

Cardiac function and tolerance to ischemia/reperfusion injury in a rat model of polycystic ovary syndrome during the postmenopausal period.

Life Sci 2020 Dec 7;262:118394. Epub 2020 Sep 7.

Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Aims: There is much controversy regarding whether cardiovascular events increase in women with polycystic ovary syndrome (PCOS) with aging. Considering the lack of possibility of certain investigations in humans, animal models of PCOS may be suitable resources to obtain the useful data needed. In this study; we aimed to investigate whether cardiac function and tolerance to ischemia/reperfusion (I/R) injury worsen in postmenopausal rats, who had PCOS at younger ages, compared to controls.

Main Methods: The hearts of aged rats with a history of PCOS and their controls were isolated and perfused in a Langendorff apparatus. Values of hemodynamic parameters, including left ventricular systolic pressure (LVSP), left ventricular developed pressure (LVDP), rate pressure product (RPP) and peak rates of positive and negative changes in left ventricular pressure (±dp/dt) were recorded using a power lab system. Blood serum levels of total testosterone (TT) and estradiol (E2) were determined by ELISA kits. Generalized Estimating Equation Model and t-student unpaired test results were used to compare the findings documented between two groups.

Key Findings: No statistically significant differences were observed in hemodynamic parameters of the heart including, LVSP, LVDP, RPP and ±dp/dt, between the rats of two groups of study, at baseline or before ischemia and after I/R. Nor were any significant differences observed in the levels of two hormones between the two groups (p > 0.05).

Significance: History of PCOS during reproductive ages should not be considered an important risk factor for reduction in cardiac contractile function or less tolerance to I/R injury during the postmenopausal period.
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http://dx.doi.org/10.1016/j.lfs.2020.118394DOI Listing
December 2020

Online analysis of local field potentials for seizure detection in freely moving rats.

Iran J Basic Med Sci 2020 Feb;23(2):173-177

Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Objectives: Seizure detection during online recording of electrophysiological parameters is very important in epileptic patients. In the present study, online analysis of field potential recordings was used for detecting spontaneous seizures in epileptic animals.

Materials And Methods: Epilepsy was induced in rats by pilocarpine injection. During the chronic period of the pilocarpine model, local field potential (LFP) recording was run for at least 24 hr. At the same time, video monitoring of the animals was done to determine the real time of seizure occurrence. Both power and sample entropy of LFP were used for online analysis.

Results: Obtained results showed that changes in LFP power are a better index for seizure detection. In addition, when we used one hundred consecutive epochs (each epoch equals 10 ms) of LFP for data analysis, the best detection was achieved.

Conclusion: It may be suggested that power is a suitable parameter for online analysis of LFP in order to detect the spontaneous seizures correctly.
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http://dx.doi.org/10.22038/IJBMS.2019.38722.9183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211346PMC
February 2020

The role of dopamine D-like receptors in a "depotentiation-like effect" of deep brain stimulation in kindled rats.

Brain Res 2020 07 3;1738:146820. Epub 2020 Apr 3.

Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; Institute for Brain Sciences and Cognition, Tarbiat Modares University, Tehran, Iran. Electronic address:

The mechanisms involved in the anti-seizure effects of low-frequency stimulation (LFS) have not been completely determined. However, G-protein-coupled receptors, including D-like receptors, may have a role in mediating these effects. In the present study, the role of D-like receptors in LFS' anti-seizure action was investigated. Rats were kindled with semi-rapid (6 stimulations per day), electrical stimulation of the hippocampal CA1 area. In LFS-treated groups, subjects received four trials of LFS at 5 min, 6 h, 24 h, and 30 h following the last kindling stimulation. Each LFS set occurred at 5 min intervals, and consisted of 4 trains. Each train contained 200, 0/1 ms long, monophasic square wave pulses at 1 Hz. Haloperidol (D-like receptors antagonist, 2 µm) and/or bromocriptine (D-like receptors agonist 2 µg/µlit) were microinjected into the lateral ventricle immediately after the last kindling, before applying LFS. Obtained results showed that applying LFS in fully-kindled subjects led to a depotentiation-like decrease in kindling-induced potentiation and reduced the amplitude and rise slope of excitatory and inhibitory post-synaptic currents in whole-cell recordings from CA1 pyramidal neurons. In addition, LFS restored the kindling-induced, spatial learning and memory impairments in the Barnes maze test. A D-like receptor antagonist inhibited these effects of LFS, while a D-like receptor agonist mimicked these effects. In conclusion, a depotentiation-like mechanism may be involved in restoring LFS' effects on learning and memory, and synaptic plasticity. These effects depend on D-like receptors activity.
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http://dx.doi.org/10.1016/j.brainres.2020.146820DOI Listing
July 2020

Allergen-induced anxiety-like behavior is associated with disruption of medial prefrontal cortex - amygdala circuit.

Sci Rep 2019 12 20;9(1):19586. Epub 2019 Dec 20.

Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Anxiety is prevalent in asthma, and is associated with disease severity and poor quality of life. However, no study to date provides direct experimental evidence for the effect of allergic inflammation on the structure and function of medial prefrontal cortex (mPFC) and amygdala, which are essential regions for modulating anxiety and its behavioral expression. We assessed the impact of ovalbumin (OVA)-induced allergic inflammation on the appearance of anxiety-like behavior, mPFC and amygdala volumes using MRI, and the mPFC-amygdala circuit activity in sensitized rats. Our findings exhibited that the OVA challenge in sensitized rats induced anxiety-like behavior, and led to more activated microglia and astrocytes in the mPFC and amygdala. We also found a negative correlation between anxiety-like behavior and amygdala volume. Moreover, OVA challenge in sensitized rats was associated with increases in mPFC and amygdala activity, elevation of amygdala delta-gamma coupling, and the enhancement of functional connectivity within mPFC-amygdala circuit - accompanied by an inverted direction of information transferred from the amygdala to the mPFC. We indicated that disrupting the dynamic interactions of the mPFC-amygdala circuit may contribute to the induction of anxiety-related behaviors with asthma. These findings could provide new insight to clarify the underlying mechanisms of allergic inflammation-induced psychiatric disorders related to asthma.
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http://dx.doi.org/10.1038/s41598-019-55539-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925103PMC
December 2019

Distraction of olfactory bulb-medial prefrontal cortex circuit may induce anxiety-like behavior in allergic rhinitis.

PLoS One 2019 11;14(9):e0221978. Epub 2019 Sep 11.

Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Allergic rhinitis is a chronic inflammatory disease of the upper respiratory tract, which is associated with high incidence of anxiety symptom. There is evidence that medial prefrontal cortex modulates anxiety-related behaviors and receives projections from olfactory bulb. Since olfactory dysfunction has been reported in allergic rhinitis, we aimed to evaluate anxiety-like behavior and oscillations of olfactory bulb-medial prefrontal cortex circuit in an animal model of allergic rhinitis. The number of open arm entries in elevated zero maze was significantly reduced in sensitized rats exposed to intranasal ovalbumin compared to the control group, which was indicating the enhancement of anxiety-like behavior in allergic rhinitis animals. Analysis of local field potentials in olfactory bulb and medial prefrontal cortex during immobility and exploration state showed that anxiety-like behavior induced by allergic rhinitis was in association with increased activity of medial prefrontal cortex and enhancement of olfactory bulb-medial prefrontal cortex coupling in delta and theta bands. Moreover, in allergic rhinitis animals, theta strongly coordinates local gamma activity in olfactory bulb and medial prefrontal cortex, which means to have a strong local theta/gamma coupling. We suggested that disruption of olfactory bulb-medial prefrontal cortex circuit due to allergic reactions might have a governing role for inducing anxiety-like behavior in the allergic rhinitis experimental model.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0221978PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738655PMC
March 2020

Modulating proteoglycan receptor PTPσ using intracellular sigma peptide improves remyelination and functional recovery in mice with demyelinated optic chiasm.

Mol Cell Neurosci 2019 09 2;99:103391. Epub 2019 Jul 2.

Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; Department of Brain and Cognitive Sciences, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. Electronic address:

Multiple sclerosis (MS) is an autoimmune disease characterized by myelin and axonal damage in the central nervous system (CNS). Glial scar which is a hallmark of MS contains repair inhibitory molecules including chondroitin sulfate proteoglycans (CSPGs). CSPGs inhibit repair of damaged area through various receptors including protein tyrosine phosphatase sigma (PTPσ). In the current study we use intracellular sigma peptide (ISP), an inhibitor of PTPσ signaling, in LPC-induced focal demyelination of mouse optic chiasm. ISP treatment resulted in decreased demyelination, reduced astrogliosis, and increased newly generated oligodendrocytes which subsequently led to enhanced remyelination. Analyzing of electrophysiological (as performed by visual evoked potential recording) and behavioral (performed by visual cliff test) outcomes showed that ISP-treatment improved the integrity of optic pathway as well as the visual acuity. When ISP was administrated only during the repair phase, histological, electrophysiological and behavioral studies showed its regenerative effect. Our results demonstrated the possibility of using ISP as a new strategy to inhibit PTPσ for myelin protection, myelin repair in demyelinated axons, and functional neural pathway conductivity restoration in patients suffering from MS.
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http://dx.doi.org/10.1016/j.mcn.2019.103391DOI Listing
September 2019

The effects of prenatal androgen exposure on cardiac function and tolerance to ischemia/reperfusion injury in male and female rats during adulthood.

Life Sci 2019 Jul 18;229:251-260. Epub 2019 May 18.

Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Aims: Cardiovascular diseases may originate from suboptimal intrauterine environments. We aimed to examine the effects of prenatal androgen exposure (PAE) on heart basal hemodynamic parameters and tolerance to ischemia/reperfusion (I/R) injury, in PAE adult females and males.

Main Methods: Pregnant Wistar rats in the experimental group (n = 8) received 5 mg of testosterone (s.c. injection) on the 20th day of pregnancy, while controls received solvent. The hearts of adult female and male offspring were isolated and perfused in a Langendorff apparatus, values of left ventricular systolic pressure(LVSP), left ventricular developed pressure(LVDP), rate pressure product(RPP) and peak rates of positive and negative changes in left ventricular pressure(±dp/dt) were recorded using a power lab system.

Key Findings: At baseline, PAE adult males demonstrated significant higher values of LVSP, LVDP, RPP and ± dp/dt, compared to controls and PAE adult females (p < 0.05), while PAE adult females showed no significant differences compared to controls. In PAE adult males, LVSP, LVDP, RPP and ± dp/dt had significant decreasing trends per phases after I/R, compared to their controls and PAE females, while these decreasing trends were not statistically significant in PAE adult female rats vs. their controls.

Significance: The impact of prenatal androgen exposure on adulthood cardiac function and tolerance to I/R is gender dependent, which may be partly explained by different cardiac effects of hyperandrogenism in males versus females. After prenatal androgen exposure, the baseline hemodynamic parameters of the hearts of adult males are increased; although they had less tolerance to I/R, findings however not observed in females.
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http://dx.doi.org/10.1016/j.lfs.2019.05.044DOI Listing
July 2019

Brain wave disturbance and cognitive impairment after CPR.

Med Hypotheses 2019 May 27;126:129-130. Epub 2019 Mar 27.

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

Cognitive impairment (CI) is a common morbidity after cardio-pulmonary resuscitation (CPR) with long time persistence. Brain hypoxia is believed to be the main but not the single etiology of post CPR cognitive impairment. Theta and lower theta waves of the EEG have essential role in proper functioning of the memory performance. Both endotracheal intubation and atropine administration in CPR process can abolish these waves. We hypothesize that CI in CPR survivors can be caused by disturbance in aforementioned waves due to endotracheal intubation and atropine administration.
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http://dx.doi.org/10.1016/j.mehy.2019.03.009DOI Listing
May 2019

First Experience with Extracorporeal Membrane Oxygenation in Iran, under Difficult Conditions.

J Tehran Heart Cent 2018 Oct;13(4):166-172

Tracheal Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Extracorporeal membrane oxygenation (ECMO) provides hemodynamic and oxygenation support in critical conditions. The commencement of this modality in Iran coincided with severe economic constraints across Iran. This retrospective study was performed in Masih Daneshvari Medical Center from 2010 to 2015, during which period, sanction-related limitations in the import of equipment prompted us to integrate a Medtronic or Stöckert head pump console into a Maquet ECMO Oxygenator so as to sustain the ECMO program. Comparisons were performed between successful and unsuccessful ECMO procedures and survivors. Factors associated with unsuccessful ECMO were evaluated with a multivariate logistic regression. Thirty-three (68.8%) patients were male and 15 (31.2%) were female. The mean age of the patients was 35±16.6 years. Thirty-seven (77.1%) patients were weaned off ECMO successfully; the rate was higher than that in previous studies. Totally, 35.4% of the study population survived to hospital discharge. The most common cause of death in all the ECMO patients who were successfully weaned was sepsis. The most common cause of death in the patients who underwent unsuccessful ECMO was multisystem organ failure. The mean ECMO support time was 53.37±46.26 hours. The patients who were alive at discharge were significantly younger (25.5±14.5 vs. 40.2±15.5 y; P=0.002) and had a significantly lower ECMO duration (24 [25-75% interquartile: 18.5-36] vs. 48 [25-75% interquartile: 24-72] h; P=0.044) than the non-survivors. An assembly of ECMO components from different companies could be done safely, at least for a short period of time.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450813PMC
October 2018

Protective effect of heart rate variability biofeedback on stress-induced lung function impairment in asthma.

Respir Physiol Neurobiol 2019 04 26;262:49-56. Epub 2019 Jan 26.

Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address:

Psychological stress can provoke airway constriction in asthmatic patients, which may be because of autonomic nervous system dysfunction in asthma. We investigated the effect of enhancing respiratory sinus arrhythmia using heart rate variability biofeedback (HRV-BF) on spirometry performance and HRV indices during stress induced by Stroop Color-Word interference test in asthmatic patients and healthy volunteers. Stress caused decrease in FEV1%, FVC%, and PEF% compared to baseline in asthmatic patients, but not in healthy subjects. A single short duration episode of HRV-BF not only had a protective effect on stress-induced airway constriction, but also significantly augmented the level of FEV1% and FVC% as compared with their own baseline. Also, there was a significant correlation between HRV changes and the augmentation of spirometry performance in asthmatic patients receiving HRV-BF. Our findings indicated that even a single short duration episode of HRV-BF can decrease susceptibility to stress-induced lung function impairment in patients with asthma, which may be through the modulation of respiratory sinus arrhythmia.
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http://dx.doi.org/10.1016/j.resp.2019.01.011DOI Listing
April 2019

The inhibitory effect of different patterns of low frequency stimulation on neuronal firing following epileptiform activity in rat hippocampal slices.

Brain Res 2019 03 9;1706:184-195. Epub 2018 Nov 9.

Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; Institute for Brain Sciences and Cognition, Tarbiat Modares University, Tehran, Iran. Electronic address:

Low frequency stimulation (LFS) has inhibitory effect on hyperexcitability during epileptic states. However, knowledge is lacking about LFS patterns that can exert an optimal antiepileptic effect. In this study, the effect of different numbers of pulses and current intensities of 1 Hz LFS applied at various time points of epileptiform activity was evaluated in high-K model of epileptiform activity (EA). LFS was applied to the Schaffer collaterals, and changes in the excitability of CA1 pyramidal neurons were measured using whole-cell patch-clamp recording. Six hundred and 900 pulses of LFS at two current intensities (equal to and 1.5 times greater than the current intensity sufficient to elicit a 5 mV EPSP) administered at the beginning of EA revealed a stronger LFS inhibitory effect on EA-induced neuronal hyperexcitability when applied at higher pulse number and current intensity. LFS900 (high intensity) significantly hyperpolarized the membrane potential after a high-K ACSF washout, reduced the frequency of spontaneous action potentials during EA, and attenuated neuronal firing frequency after high-K ACSF washout. Moreover, applying LFS900 (high intensity) before EA induction and 8-10 min after EA initiation could not significantly affect neuronal hyperexcitability, compared to its application at the beginning of EA. This study's findings also offered long-term depression (LTD) as a probable mechanism for LFS' inhibitory role on EA-induced neuronal hyperexcitability. Therefore, the application of LFS (1 Hz) at 900 pulses and greater current intensity at the beginning of EA can exert a strong inhibitory effect on EA-induced neuronal hyperexcitability.
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http://dx.doi.org/10.1016/j.brainres.2018.11.012DOI Listing
March 2019

Cognitive disorders in allergic rhinitis may be induced by decline of respiration entrained rhythm in the brain.

Med Hypotheses 2018 12 22;121:89-90. Epub 2018 Sep 22.

Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address:

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http://dx.doi.org/10.1016/j.mehy.2018.09.037DOI Listing
December 2018

Acute morphine administration alters the power of local field potentials in mesolimbic pathway of freely moving rats: Involvement of dopamine receptors.

Neurosci Lett 2018 11 13;686:168-174. Epub 2018 Sep 13.

Department of Cognitive Neuroscience, Institute for Cognitive Science Studies (ICSS), Tehran, Iran. Electronic address:

Increasing number of evidence support the role of ventral tegmental area (VTA) and nucleus accumbens (NAc) in mediating the opiate effects as the two critical components of brain reward pathway. It is believed that VTA to NAC dopaminergic projections mediate the reinforcing effects induced by opioid drugs. Although numerous studies have investigated mechanisms of reward processing in these brain regions, alterations of local field potentials (LFPs), as an index of total synaptic currents, has not been previously addressed. In the present study, thin metal electrodes were implanted in both VTA and shell sub-region of NAc to simultaneously record the spontaneous LFPs in freely moving rats. After one week recovery period, a single dose of morphine was systemically administered and the LFP recording was performed 15, 30, 45 and 60 post-injection. Also, in order to assess the role of dopamine system, two groups of animals were pre-treated by selective antagonists of dopamine type-1 and type-2 receptors 15 min prior to morphine injection. The obtained results indicated that in VTA, acute morphine administration potentiates the power of all LFP frequency bands (i.e. delta, theta, alpha, beta and gamma). However, in NAc shell, theta wave was significantly attenuated by morphine and other components were not affected. In addition, pre-treatment with both antagonists prevented the observed effect of morphine on LFP power suggesting the involvement of dopamine receptors in this process. Future studies should address mechanisms of dopamine-morphine interactions. It is also valuable to focus on acute and chronic effects of morphine on LFP power and assessment of the observed effects following naloxone challenge.
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http://dx.doi.org/10.1016/j.neulet.2018.09.016DOI Listing
November 2018

Low Frequency Electrical Stimulation Attenuated The Epileptiform Activity-Induced Changes in Action Potential Features in Hippocampal CA1 Pyramidal Neurons.

Cell J 2018 Oct 15;20(3):355-360. Epub 2018 May 15.

Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic

Objective: Electrical low frequency stimulation (LFS) is a new therapeutic method that moderates hyperexcitability during epileptic states. Seizure occurrence is accompanied by some changes in action potential (AP) features. In this study, we investigated the inhibitory action of LFS on epileptiform activity (EA) induced-changes in AP features in hippocampal CA1 pyramidal neurons.

Materials And Methods: In this experimental study, we induced EA in hippocampal slices by increasing the extracellular potassium (K+) concentration to 12 mM. LFS (1 Hz) was applied to the Schaffer collaterals at different pulse numbers (600 and 900) at the beginning of the EA. Changes in AP features recorded by whole-cell patch clamp recording were compared using phase plot analysis.

Results: Induction of EA depolarized membrane potential, decreased peak amplitude, as well as the maximum rise and decay slopes of APs. Administration of 1 Hz LFS at the beginning of EA prevented the above mentioned changes in AP features. This suppressive effect of LFS depended on the LFS pulse number, such that application of 900 pulses of LFS had a stronger recovery effect on AP features that changed during EA compared to 600 pulses of LFS. The constructed phase plots of APs revealed that LFS at 900 pulses significantly decreased the changes in resting membrane potential (RMP), peak amplitude, and maximum rise and decay slopes that appeared during EA.

Conclusion: Increasing the numbers of LFS pulses can magnify its inhibitory effects on EA-induced changes in AP features.
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http://dx.doi.org/10.22074/cellj.2018.5443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6004994PMC
October 2018

Variable ventilation decreases airway responsiveness and improves ventilation efficiency in a rat model of asthma.

Respir Physiol Neurobiol 2018 09 15;255:39-42. Epub 2018 May 15.

Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address:

The optimal ventilation strategy in patients receiving mechanical ventilation for severe asthma remains unclear. The effect of conventional ventilation (with constant tidal volume and respiratory rate) and variable ventilation (with the same average but variable tidal volume and respiratory rate) on peak airway pressure and airway exacerbation induced by increasing doses of methacholine was compared in a rat model of asthma. The respiratory rate and tidal volume data were obtained from a spontaneously breathing intact rat during immobility using a whole-body plethysmograph. Peak airway pressure and airway responsiveness to cumulative doses of methacholine were significantly affected by ventilation mode and they were lower in variable ventilation group than in the conventional ventilation group. Also, variable ventilation improved oxygen saturation compared to conventional ventilation. Our results indicate that variable ventilation decreases airway responsiveness and enhances ventilation efficiency in a rat model of asthma. We suggest further investigations on beneficial effects of variable ventilation strategy in mechanically ventilated patients with severe asthma.
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http://dx.doi.org/10.1016/j.resp.2018.05.007DOI Listing
September 2018

Eliminated respiration-coupled oscillations in the brain as a possible link between adenotonsillar hypertrophy and cognitive impairment.

Med Hypotheses 2018 03 31;112:63-64. Epub 2018 Jan 31.

Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Nasr Bridge, Jalal Al Ahmad Highway, Tehran, Iran. Electronic address:

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http://dx.doi.org/10.1016/j.mehy.2018.01.015DOI Listing
March 2018

Discriminating Tuberculous Pleural Effusion from Malignant Pleural Effusion Based on Routine Pleural Fluid Biomarkers, Using Mathematical Methods.

Tanaffos 2017 ;16(2):157-165

Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Background: The differential diagnosis of tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) is difficult because the biochemical profiles are similar. The present study aimed to differentiate TPE from MPE, using a decision tree and a weighted sparse representation-based classification (WSRC) method, based on the best combination of routine pleural effusion fluid biomarkers.

Materials And Methods: The routine biomarkers of pleural fluid, including differential cell count, lactate dehydrogenase (LDH), protein, glucose and adenosine deaminase (ADA), were measured in 236 patients (100 with TPE and 136 with MPE). A Sequential Forward Selection (SFS) algorithm was employed to obtain the best combination of parameters for the classification of pleural effusions. Moreover, WSRC was compared to the standard sparse representation-based classification (SRC) and the Support Vector Machine (SVM) methods for classification accuracy.

Results: ADA provided the highest diagnostic performance in differentiating TPE from MPE, with 91.91% sensitivity and 74.0% specificity. The best combination of parameters for discriminating TPE from MPE included age, ADA, polynuclear leukocytes and lymphocytes. WSRC outperformed the SRC and SVM methods, with an area under the curve of 0.877, sensitivity of 93.38%, and specificity of 82.0%. The generated flowchart of the decision tree demonstrated 87.2% accuracy for discriminating TPE from MPE.

Conclusion: This study indicates that a decision tree and a WSRC are novel, noninvasive, and inexpensive methods, which can be useful in discriminating between TPE and MPE, based on the combination of routine pleural fluid biomarkers.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749329PMC
January 2017

Effect of Low-Frequency Electrical Stimulation on the High-K-Induced Neuronal Hyperexcitability in Rat Hippocampal Slices.

Neuroscience 2018 01 11;369:87-96. Epub 2017 Nov 11.

Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address:

Low-frequency electrical stimulation (LFS) is a potential therapeutic method for epilepsy treatment. However, the effect of different LFS characteristics including the number of pulses, intensity and the time of application on its antiepileptic action has not been completely determined. In the present study, epileptiform activity (EA) was induced in hippocampal slices by high-K solution which was washed out after 20 min. The changes in the electrophysiological properties of CA1 pyramidal neurons were measured during and 30 min after EA using whole-cell patch-clamp recording. EA occurrence resulted in neuronal hyperexcitability. Application of 1-Hz LFS to the Schaffer collaterals at 600 and 900 pulses and two intensities (equal and 1.5 times more than an intensity sufficient to elicits a 5-mV EPSP) at the beginning of EA showed that 900-pulse LFS at high intensity had stronger preventing effect on high-K-induced neuronal hyperexcitability by increasing the rheobase current, utilization time, first-spike latency, delay to first-rebound action potential and decreasing the number of rebound action potential. In addition, application of high-intensity 900-pulse LFS had better inhibitory effect on the neuronal hyperexcitability when applied at the beginning of EA compared to its administration before or at 8-10 min after EA. Therefore, it may suggest the inhibitory action of LFS on the neuronal hyperexcitability is augmented by increasing its number of pulses and intensity. In addition, there is a time window for LFS application so that its application at the beginning of EA has better inhibitory effect.
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http://dx.doi.org/10.1016/j.neuroscience.2017.11.012DOI Listing
January 2018

Effect of Rho-kinase inhibition on complexity of breathing pattern in a guinea pig model of asthma.

PLoS One 2017 31;12(10):e0187249. Epub 2017 Oct 31.

Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Asthma represents an episodic and fluctuating behavior characterized with decreased complexity of respiratory dynamics. Several evidence indicate that asthma severity or control is associated with alteration in variability of lung function. The pathophysiological basis of alteration in complexity of breathing pattern in asthma has remained poorly understood. Regarding the point that Rho-kinase is involved in pathophysiology of asthma, in present study we investigated the effect of Rho-kinase inhibition on complexity of respiratory dynamics in a guinea pig model of asthma. Male Dunkin Hartley guinea pigs were exposed to 12 series of inhalations with ovalbumin or saline. Animals were treated by the Rho-kinase inhibitor Y-27632 (1mM aerosols) prior to each allergen challenge. We recorded respiration of conscious animals using whole-body plethysmography. Exposure to ovalbumin induced lung inflammation, airway hyperresponsiveness and remodeling including goblet cell hyperplasia, increase in the thickness of airways smooth muscles and subepithelial collagen deposition. Complexity analysis of respiratory dynamics revealed a dramatic decrease in irregularity of respiratory rhythm representing less complexity in asthmatic guinea pigs. Inhibition of Rho-kinase reduced the airway remodeling and hyperreponsiveness, but had no significant effect on lung inflammation and complexity of respiratory dynamics in asthmatic animals. It seems that airway hyperresponsiveness and remodeling do not significantly affect the complexity of respiratory dynamics. Our results suggest that inflammation might be the probable cause of shift in the respiratory dynamics away from the normal fluctuation in asthma.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0187249PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663484PMC
November 2017

Effect of airway remodeling and hyperresponsiveness on complexity of breathing pattern in rat.

Respir Physiol Neurobiol 2018 01 15;247:65-70. Epub 2017 Sep 15.

Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address:

The complexity of respiratory dynamics is decreased, in association with disease severity, in patients with asthma. However, the pathophysiological basis of decreased complexity of breathing pattern in asthma is not clear. In the present study, we investigated the effect of airway remodeling and hyperresponsiveness induced by repeated bronchoconstriction (using methacholine) on breathing pattern in rats with or without allergen-induced sensitization. Entropy analysis of respiratory variability showed decreased irregularity (less complexity) of respiratory rhythm in this rat model of asthma. Airway remodeling and hyperresponsiveness induced by repeated bronchoconstriction also led to increased regularity of respiratory dynamics in sensitized rats. However, these airway alterations had no significant effect on the complexity of breathing pattern in non-sensitized rats. Our results indicate that mechanical respiratory alterations cannot per se attenuate the complexity of respiratory dynamics, unless there is an underlying inflammation. We suggest further studies on underlying mechanisms of breathing variability with focus on respiratory control alterations due to airway inflammation.
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http://dx.doi.org/10.1016/j.resp.2017.09.007DOI Listing
January 2018

Complexity Analysis of Respiratory Dynamics.

Am J Respir Crit Care Med 2017 07;196(2):247-248

4 University College London London, United Kingdom.

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http://dx.doi.org/10.1164/rccm.201701-0026LEDOI Listing
July 2017

Bronchoconstriction Induces Structural and Functional Airway Alterations in Non-sensitized Rats.

Lung 2017 04 26;195(2):167-171. Epub 2016 Dec 26.

Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Nasr Bridge, Jalal Al Ahmad Highway, Tehran, Iran.

The impact of mechanical forces on pathogenesis of airway remodeling and the functional consequences in asthma remains to be fully established. In the present study, we investigated the effect of repeated bronchoconstriction induced by methacholine (MCh) on airway remodeling and airway hyperresponsiveness (AHR) in rats with or without sensitization to an external allergen. We provide evidence that repeated bronchoconstriction, using MCh, alone induces airway inflammation and remodeling as well as AHR in non-allergen-sensitized rats. Also, we found that the airways are structurally and functionally altered by bronchoconstriction induced by either allergen or MCh in allergen-sensitized animals. This finding provides a new animal model for the development of airway remodeling and AHR in mammals and can be used for studying the complex reciprocal relationship between bronchoconstriction and airway inflammation. Further studies on presented animal models are required to clarify the exact mechanisms underlying airway remodeling due to bronchoconstriction and the functional consequences.
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http://dx.doi.org/10.1007/s00408-016-9970-4DOI Listing
April 2017

Role of shear stress in ventilator-induced lung injury.

Lancet Respir Med 2016 08 20;4(8):e41-e42. Epub 2016 Jun 20.

Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran 1411713116, Iran. Electronic address:

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http://dx.doi.org/10.1016/S2213-2600(16)30159-XDOI Listing
August 2016

Classification of Asthma Based on Nonlinear Analysis of Breathing Pattern.

PLoS One 2016 29;11(1):e0147976. Epub 2016 Jan 29.

Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Normal human breathing exhibits complex variability in both respiratory rhythm and volume. Analyzing such nonlinear fluctuations may provide clinically relevant information in patients with complex illnesses such as asthma. We compared the cycle-by-cycle fluctuations of inter-breath interval (IBI) and lung volume (LV) among healthy volunteers and patients with various types of asthma. Continuous respiratory datasets were collected from forty age-matched men including 10 healthy volunteers, 10 patients with controlled atopic asthma, 10 patients with uncontrolled atopic asthma, and 10 patients with uncontrolled non-atopic asthma during 60 min spontaneous breathing. Complexity of breathing pattern was quantified by calculating detrended fluctuation analysis, largest Lyapunov exponents, sample entropy, and cross-sample entropy. The IBI as well as LV fluctuations showed decreased long-range correlation, increased regularity and reduced sensitivity to initial conditions in patients with asthma, particularly in uncontrolled state. Our results also showed a strong synchronization between the IBI and LV in patients with uncontrolled asthma. Receiver operating characteristic (ROC) curve analysis showed that nonlinear analysis of breathing pattern has a diagnostic value in asthma and can be used in differentiating uncontrolled from controlled and non-atopic from atopic asthma. We suggest that complexity analysis of breathing dynamics may represent a novel physiologic marker to facilitate diagnosis and management of patients with asthma. However, future studies are needed to increase the validity of the study and to improve these novel methods for better patient management.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0147976PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4732950PMC
July 2016