Shefa Neuroscience Research Center

Tehrān, Iran

Shefa Neuroscience Research Center

Tehrān, Iran
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Coulon P.,Seattle Childrens Research Institute | Gorji A.,University of Munster | Gorji A.,Shefa Neuroscience Research Center
Trends in Pharmacological Sciences | Year: 2016

Novel psychoactive substances flood worldwide markets faster than they can be banned. Legislators struggle to find a balance between free availability, prescription systems, and criminalisation, while physicians try to balance risks and benefits of drug treatment and identify drug abuse - a tightrope walk. Classification of psychoactive substances is central to these decision-making processes but existing classifications rely on unrelated, inconsistent, and shifting guidelines that categorise drugs by chemical structure, toxicity, or addictive potency. We propose that a new categorisation of drugs based on neurobiological mechanisms of action may help to simplify the regulation of drug use, delivers a neurobiological context, and streamlines classification and future regulatory directions. We provide guidelines to distinguish between drug abuse and treatment and to navigate the controversies over legalising or banning drugs. Finally, we comment on the role neuroscientific research can play in the future to solve imminent problems in this highly important field. © 2016 Elsevier Ltd.


Eickhoff M.,University of Munster | Kovac S.,University of Munster | Kovac S.,University College London | Shahabi P.,Shefa Neuroscience Research Center | And 7 more authors.
Experimental Neurology | Year: 2014

There is unequivocal electrophysiological evidence that spreading depression (SD) can trigger epileptiform field potentials. In vitro experiments on human brain tissues indicated that γ-aminobutyric acid (GABA)-mediated inhibition prevented this process. Intra- and extracellular recordings of bioelectrical activities were performed in the rodent neocortex, hippocampus and amygdala after perfusion of low concentrations of the GABAA antagonist bicuculline and induction of SD by KCl application. Induction of SD in combined amygdala-hippocampus-cortex slices pre-treated with low concentration of bicuculline triggered epileptiform burst discharges in cortical as well as subcortical brain structures. Propagation of SD significantly depolarized the membrane, decreased the amplitude and duration of action potentials (APs) and after-hyperpolarization as well as the neuronal membrane input resistance and the amplitude of threshold potentials. Ten to twenty minutes after induction of SD, the pattern of APs changed from regular firing to a series of APs riding on an underlying paroxysmal depolarization shift before the appearance of typical ictaform activities. Changes of characteristic features of APs occurred after SD persisted during the appearance of epileptiform activities. These results indicate that SD increases neuronal excitability and facilitates synchronization of neuronal discharges in the presence of partial disinhibition of neuronal tissues. Our findings might explain the occurrence of seizures in neurological disorders with partial impairment of inhibitory tone, such as brain ischemia and epilepsy. © 2013 Elsevier Inc.


Ghaemi A.,Shefa Neuroscience Research Center | Ghaemi A.,Golestan University of Medical Sciences | Sajadian A.,Shefa Neuroscience Research Center | Khodaie B.,Shefa Neuroscience Research Center | And 7 more authors.
Molecular Neurobiology | Year: 2016

The release of inflammatory mediators following cortical spreading depression (CSD) is suggested to play a role in pathophysiology of CSD-related neurological disorders. Toll-like receptors (TLR) are master regulators of innate immune function and involved in the activation of inflammatory responses in the brain. TLR3 agonist poly I:C exerts anti-inflammatory effect and prevents cell injury in the brain. The aim of the present study was to examine the effect of systemic administration of poly I:C on the release of cytokines (TNF-α, IFN-γ, IL-4, TGF-β1, and GM-CSF) in the brain and spleen, splenic lymphocyte proliferation, expression of GAD65, GABAAα, GABAAβ as well as Hsp70, and production of dark neurons after induction of repetitive CSD in juvenile rats. Poly I:C significantly attenuated CSD-induced production of TNF-α and IFN-γ in the brain as well as TNF-α and IL-4 in the spleen. Poly I:C did not affect enhancement of splenic lymphocyte proliferation after CSD. Administration of poly I:C increased expression of GABAAα, GABAAβ as well as Hsp70 and decreased expression of GAD65 in the entorhinal cortex compared to CSD-treated tissues. In addition, poly I:C significantly prevented production of CSD-induced dark neurons. The data indicate neuroprotective and anti-inflammatory effects of TLR3 activation on CSD-induced neuroinflammation. Targeting TLR3 may provide a novel strategy for developing new treatments for CSD-related neurological disorders. © 2014, Springer Science+Business Media New York.


Martens-Mantai T.,University of Munster | Speckmann E.-J.,University of Munster | Gorji A.,University of Munster | Gorji A.,Shefa Neuroscience Research Center
Synapse | Year: 2014

Propagation of cortical spreading depression (CSD) to the subcortical structures could be the underlying mechanism of some neurological deficits in migraine with aura. The entorhinal cortex (EC) as a gray matter bridge between the neocortex and subcortical regions plays an important role in this propagation. In vitro combined neocortex-hippocampus brain slices were used to study the propagation pattern of CSD between the neocortex and the hippocampus. The effects of different compounds as well as tetanic electrical stimulations in the EC on propagation of CSD to the hippocampus were investigated. Repetitive induction of CSD by KCl injection in the somatosensory cortex enhanced the probability of CSD entrance to the hippocampus via EC. Local application of AMPA receptor blocker CNQX and cannabinoid receptor agonist WIN 55212-2 in EC facilitated the propagation of CSD to the hippocampus, whereas application of NMDA receptor blocker APV and GABAA receptor blocker bicuculline in this region reduced the probability of CSD penetration to the hippocampus. Application of tetanic stimulation in EC also facilitated the propagation of CSD entrance to the hippocampus. Our data suggest the importance of synaptic plasticity of EC in filtering the propagation of CSD into subcortical structures and possibly the occurrence of concomitant neurological deficits. Synapse 68:574-584, 2014. © 2014 Wiley Periodicals, Inc. Modulation of synaptic plasticity of entorhinal cortex affects propagation pattern of cortical spreading depression to the subcortical structures. © 2014 Wiley Periodicals, Inc.


Alizadeh R.,Tehran University of Medical Sciences | Hassanzadeh G.,Tehran University of Medical Sciences | Soleimani M.,Tehran University of Medical Sciences | Joghataei M.T.,Tehran University of Medical Sciences | And 4 more authors.
Journal of Chemical Neuroanatomy | Year: 2015

Introduction: Dopamine is one of the major brain neurotransmitters, and the loss of dopaminergic neurons in basal ganglia cause motor deficits in Parkinson's disease. We proposed that the difficulty in olfaction observed in the elderly may be due to an alteration in the number of dopaminergic neurons. Materials and methods: Sections were taken from olfactory bulbs of post-mortem tissue specimens of 13 humans, males and females, aged from 19 to 63 years (≤35 and ≥50 years), with no history of neurological disorders. The tissues were fixed, embedded, cut on a freezing microtome, and prepared for immunohistochemical analysis using tyrosine hydroxylase (TH) and aromatic l-amino acid decarboxylase (AADC) antibodies. The number of positive neurons was counted. Results: TH- and AADC-positive cells were present in the glomerular layer. There was no significant difference between the numbers of TH- and AADC-positive cells, in males and females, and in young and elderly individuals. The quantitative analysis revealed that the number of TH- and AADC-positive neurons were significantly higher in males than in females (P < 0.05). Moreover, there was a significant increase in the number of TH- and AADC-positive neurons in the olfactory bulbs of the elderly compared with young individuals (P < 0.05). Conclusion: Factors such as gender and age may affect the number of dopaminergic neurons, and there is a correlation between increased dopaminergic neurons and olfactory performance. Moreover, the increase in dopaminergic cells in the olfactory bulb of the elderly may indicate the existence of rostral migratory stream in adult humans. © 2015 Elsevier B.V.


Koulivand P.H.,Shefa Neuroscience Research Center | Khaleghi Ghadiri M.,Universitatsklinikum Munster | Gorji A.,Razavi Neuroscience Research Center | Gorji A.,University of Munster
Evidence-based Complementary and Alternative Medicine | Year: 2013

Lavender is traditionally alleged to have a variety of therapeutic and curative properties, ranging from inducing relaxation to treating parasitic infections, burns, insect bites, and spasm. There is growing evidence suggesting that lavender oil may be an effective medicament in treatment of several neurological disorders. Several animal and human investigations suggest anxiolytic, mood stabilizer, sedative, analgesic, and anticonvulsive and neuroprotective properties for lavender. These studies raised the possibility of revival of lavender therapeutic efficacy in neurological disorders. In this paper, a survey on current experimental and clinical state of knowledge about the effect of lavender on the nervous system is given. © 2013 Peir Hossein Koulivand et al.


Motiei-Langroudi R.,Shohada e Tajrish Hospital | Sadeghian H.,Shefa Neuroscience Research Center | Seddighi A.S.,Shohada e Tajrish Hospital
Asian Spine Journal | Year: 2014

Study Design: Case-control. Purpose: Evaluate clinical and imaging factors which may predict the risk of failure of medical therapy in patients with lumbar disc herniation (LDH). Overview of Literature: LDH is a common cause of low back pain and radicular leg pain, with a generally favorable natural course. At present, however, it is not possible to identify patients who may be candidates for surgery in an early stage of their disease by means of clinical signs or diagnostic imaging criteria. Methods: We designed a study investigating patients with untreated low back pain to assess the predictive value of demographic, clinical or imaging findings in identifying patients who finally would meet the classic current criteria for surgery. Results: Among 134 patients, 80.6% were successfully treated with conservative therapy and 19.4% finally underwent surgery. Sex, occupation, involved root level, presence of Modic changes, osteophytes or annular tears were not significantly different between the 2 groups, while cerebrospinal fluid block, Pfirrmann's grade, location of herniation with regard to the midline, and type of herniation were significantly different. Anteroposterior fragment size was significantly higher and intervertebral foramen height and thecal sac diameters were significantly lower in the surgical group. Conclusions: Although it is strongly recommended to practice conservative management at first for patients with LDH symptoms, the results of this study shows that higher Pfirrmann's grade, more laterally located discs, extrusion and protrusion herniation types, and larger fragments could predict the risk of conservative treatment failure. This way, unnecessarily prolonged conservative management (beyond 4-8 weeks) may be precluded. © 2014 by Korean Society of Spine Surgery.


Sadeghian H.,Massachusetts General Hospital | Motiei-Langroudi R.,Shefa Neuroscience Research Center
Annals of Indian Academy of Neurology | Year: 2015

Background: Migraine is a chronic and disabling disorder. Treatment of migraine often comprises of symptomatic (abortive) and preventive (prophylactic) treatment. The current drugs used in migraine prophylaxis include antidepressant drugs (Serotonin Reuptake Inhibitors, Tricyclic antidepressants), and anti-epileptic drugs (valproate, gabapentin, etc). Objective: The objective of our study was to assess the efficacy and tolerability of levetiracetam in adult migraine prophylaxis, compared to valproate and placebo. Materials and Methods: We conducted a prospective, randomized, placebo-controlled study. A total of 85 patients were randomized to receive levetiracetam 500 mg/d (n = 27), valproate 500 mg/d (n = 32) or placebo (n = 26). The patients were evaluated for treatment efficacy after 6 months. Efficacy was assessed as a more than 50% decrease in headache frequency. Results: In levetiracetam group, 17 (63.0%) patients experienced a more than 50% decrease in headache frequency, while this efficacy number was 21 (65.6%) for valproate group and 4 (15.4%) for placebo group. The difference was not statistically significant between levetiracetam and valproate, while it was significant when comparing either levetiracetam or valproate to placebo. Conclusion: Compared to placebo, levetiracetam offers improvement in headache frequency in patients with migraine. The efficacy of levetiracetam in migraine prophylaxis is comparable to currently used drugs such as valproate.


Jahromi S.R.,Shefa Neuroscience Research Center
Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia | Year: 2010

Malnutrition is a predictor of increased mortality in chronic hemodialysis (HD) patients. Various factors may contribute to malnutrition in these patients including energy and protein intake, inflammation, and comorbidity. To determine the importance of these factors in malnutrition of chronic HD patients, we studied 112 chronic HD patients in two centers was evaluated with the Dialysis Malnutrition Score (DMS) and anthropometric and biochemical indices. Seventy six (67.8%) patients were classified as malnourished. According to DMS score, poor protein intake (r= -0.34, P< 0.01), comorbidities (r= -0.24, P< 0.05), poor energy intake (r= - 0.18, P< 0.005), and inflammation (r= -0.16, P< 0.05) were significant predictors of malnutrition in descending order of importance. Multiple regression analysis showed that only poor protein intake was the explanatory variable of anthropometric measurements decline including body mass index, triceps skin fold thick-ness, mid arm circumference, mid arm muscle circumference, fat free mass, fat mass, albumin, creatinine and transferrine. None of the mentioned factors predicted the decrease of biochemical markers. We conclude that the frequency of malnutrition is high in our population and poor protein intake is the primary contributing factor for this condition. Therefore, providing enough protein may be a simple and effective way in preventing malnutrition in these patients.


Seghatoleslam M.,Mashhad University of Medical Sciences | Ghadiri M.K.,University of Munster | Ghaffarian N.,University of Munster | Speckmann E.-J.,University of Munster | And 2 more authors.
Neuroscience | Year: 2014

Cortical spreading depression (CSD) plays an important role in migraine with aura. The caudate nucleus has crucial functional interactions with brain regions likely to be important in migraine. The aim of the present in vitro study was to investigate the effect of CSD on the neuronal activity of the caudate. Intracellular recording was performed in the head of the caudate nucleus alongside of extracellular recording in Wistar rat somatosensory cortex. CSD was induced by local KCl injection. Changes in the membrane potentials of the caudate neurons began 1.2. ±. 0.2. min after CSD. The neurons of the caudate nucleus depolarized first gradually and slightly then it depolarized abruptly at nearly the same point of time of the recovery of the cortical DC potential. Action potentials (APs) reappeared after the cortical DC shift returned to the baseline. Forty-five minutes after CSD, the caudate neurons showed lower frequency of APs and larger amplitude of depolarization prior to APs. The firing pattern of the caudate neurons evoked by injection of intracellular current pulses changed from slow adapting to fast adapting after CSD. Reduced neuronal activity in the caudate after CSD may be assumed to contribute to pain as well as changes in cognition and behavior in patients with migraine. © 2014 IBRO.

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