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Introduction: Today herbal therapy has been developed as a non-invasive and less side effect treat for a variety of diseases. This study was aimed to evaluate the effect of anise oil on the hippocampal damages followed by generalized seizures. Materials & Methods: Anise oil was applied before seizure induction in rats. Anise oil was administered at different doses before induction of seizure attacks. Results: Anise oil reduced seizure severity and decreased hippocampal injuries in all treated groups. Conclusion: our findings suggest that anise oil may be a potential therapy in the generalized epilepsy.

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Introduction: The glutamergic receptors affect the synchronization of spike and wave discharges in different animal models of absence seizure. We studied the distribution of a NMDA subtype receptor in CA1 area of the hippocampus. Materials and Methods: Expression of NMDA subreceptor R2, the predominant excitatory neurotransmitter receptor in the brain, was investigated in rats suffering from absence-like seizures. Results: Rats with absence-like seizures exhibited decreased number of these NMDA subreceptors in the hippocampal formation. Conclusion: Changes of expression of these receptors in the hippocampus may be involved in cognition deficits in absence epilepsy.

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Introduction: Spreading depression (SD) is an intrinsic bioelectrical activity in central nervous system which play important role in pathophysiology of some disorders such as migraine with aura, epilepsy, transient global amnesia, and spinal cord diseases. Materials and Methods: The juvenile rats were anesthetized and recording electrodes and cannula were implanted over the brain. Repetitive cortical SD events were induced by KCl injection through the cannula. Four weeks after the KCl or Ringer injection, all rats, including control, sham and SD groups, were decapitated and the brains removed. The distribution of NR_2B subunit of NMDA receptors and the GluR1 subunit of AMPA receptors were assessed by immunohistochemical staining. Results: Expression of NR_2B receptors in the CA1 region significantly increased in the SD group compared with the sham and control group (P<0.05). Also expression of GluR1 receptors in the CA1 and CA3 regions significantly increased in the SD group (P<0.01). Conclusion: Our result showed that SD enhanced expression of the NR2B subunit of NMDA receptors and the GluR1 subunit of AMPA receptors in various regions of the juvenile rat brain.

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Introduction: Spreading depression (SD) is a pathophysiological phenomenon, which induced as consequence of ischemia, cerebral hemorrhage and cerebral injury. SD roles in some clinical disorders, including migraine aura, epilepsy, head injury and transient global amnesia, have been documented. SD is a neural hyperactivity, which slowly spread in the brain, passed through neurons or astrocyte, change blood volume, cell metabolism and distribute cell ionic balance. SD is accompanied by a transient hyperactivity, which continues by neuronal depression and hyperexcitability. Conclusion: Various investigation on animal and human brains showed enhancement in NMDA, AMPA, GABA as well as serotonin after SD. This review focuses on wide range of investigation on excitatory and inhibitory neurotransmitters after SD.

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Introduction: Juvenile Myoclonic Epilepsy (JME) is a generalized epileptic syndrome. Age of onset is usually between 12 to 18 years. JME consists of myoclonic jerks, generalized tonic-clonic seizures (GTCs) and typical absence attacks. EEG shows characteristic changes in JME. Long term video-electroencephalography monitoring (VEM) is a helpful diagnostic procedure in the diagnosis of patient with unclear history or EEG findings. In the current study, we aimed to evaluate the role of VEM in diagnosis of refractory epileptic patients. Materials and Methods: This study is retrospective and descriptive on patients of Epilepsy Monitoring Unit of Razavi Hospital, Mashhad, Iran between March 2011 and March 2012. Telephone interview was scheduled 6-18 months after discharge to evaluate results of VEM on the frequency of seizures, the therapeutic regimes and patients’ quality of life. Results: 24 cases with diagnosis of JME were chosen among 250 patients who were admitted with refractory epilepsy. Fourteen of them were female. The average age of patients was 24 years old and the average duration of the seizure attacks was 12.97 years. The mean frequency of GTCs was 2.76 attacks per month and after VEM and proper treatment, it decreased to 0.27 attacks per month. Conclusion: VEM is a helpful diagnostic procedure for evaluating of refractory JME epileptic patients.

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Introduction: There are some reports on the antiepileptic effects of genus Ferula in the traditional Persian medicine. Due to the side effects of common antiepileptic drugs, effective compounds with fewer side effects are needed. The present study examined the anticonvulsive effects of the methanol extract of Ferula in seizures induced by maximum electroshock (MES) and pentylenetetrazol (PTZ) in mice. Materials and Methods: Thirty minutes before the induction of seizures, sixty mice were divided into six groups group I: solvent (10 mg/kg control group), group II: ethosuximide (150 mg/kg as positive control group for PTZ), group III: phenytoin (25 mg/kg as positive control group for MES) and the fourth, fifth, and sixth groups: the methanol extract of Ferula (100, 250, 500 mg/kg). Results: The methanol extract of Ferula did not inhibit the occurrence of seizures induced by PTZ and MES, but significantly increased the latency time in the PTZ model. Conclusion: It seems that the methanol extract of Ferula has different effects in various models of seizures and further investigation is needed.

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Introduction: In spite of several decades of research, the technology of neuronal stimulation only in recent years has become the focus of the treatment of different neurological disorders. The potential use of stimulation of the neuronal tissues ranges from the spinal cord to different brain regions as well as to the implantations of cochlear system and bionic eyes. Electrical high-frequency deep brain stimulation (DBS) was developed as an alternative option to treat a few neurological disorders. However, with advancing in surgical procedures, technologies and safeties, the applications of DBS are expanding not only for therapeutic purposes but also for research. Although the exact mechanisms of actions are not fully understood, the outcome of the ongoing research and clinical trials are promising. DBS has been used to treat the essential tremor since 1997, Parkinson’s disease (PD) since 2002 and dystonia since 2003. It has also been used to treat various psychological disorders, including major depression. Conclusion: Although the therapeutic effect of DBS in PD is well established, in other diseases, such as epilepsy, the outcome is still unclear and ambiguous. This article is a review of the efficacy of DBS in PD, epilepsy as well as in obsessive compulsive disorder.

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Introduction: The ability to induce pluripotency in somatic cells by reprogramming factors offers new opportunities for drug discovery and cell therapy. Induced pluripotent stem cells have the potential to differentiate to various cell types, such as neural and glial cells. Astrocytes, the major glial cells of the central nervous system, play an important role in the function of the brain by regulating of extracellular ions and neurotransmitters, feeding and protection of neurons as well as modulating the activity of microglia. Microglia over-activation can be resulted in brain inflammation with subsequent susceptibility to epileptic seizures. Hypothesis: For many years, embryonic Stem cell transplantation has been examined to prevent seizure attacks in epilepsy. These studies have indicated that adult cells from patient have the ability to be transformed to embryonic stage and convert to a pluripotent stem cell by using some Transcription factors (such as Oct4, Sox2, Nanog, Rex1, Klf, c-Myc and LIN28). Accordingly, fibroblasts from an epileptic have also been reprogrammed to embryonic stage. The resulting iPS cells are isogenic to patient and are able to transform to neurons or glia in a suitable culture condition. Previous studies on ES cell therapy have focused more on neurons than astrocytes. Astrocytes, by secretion of glial cell-derived neurotrophic factor, not only regulate the different microglial activities, such as proliferation, migration and cell adhesion, but can also reduce destructive effects of microglia. Conclusion: In this hypothesis, we suggest a reprogramming system for generating functional astrocyte from human pluripotent stem cell in the presence of neural growth factors. We hypothesize that these cells might reduce neuroinflammation induced by microglia and subsequent susceptibility to seizure. The reprogrammed cells could be used in cell replacement therapy of epilepsy.

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Anxiety disorder is characterized by constant feelings of worry, excitation or alternative panic attacks. Anxiety becomes a disorder when the feelings are repeated or severe and are produced by insignificant things or nothing at all and interfere with our functioning. Epilepsy is determined as two or more unprovoked seizures. Many recent epidemiological studies have found the prevalence of depression and anxiety to be higher in people with epilepsy than in people without epilepsy. There is a relationship between the appearance of epileptics and levels of depression and anxiety. Almost 35% of people with epilepsy suffer from depression and anxiety. Depression and anxiety may lead to suicidal ideation or efforts and drug addiction and require further attention because they carry the risk of reduced quality of life. These experiences are also likely to increase the unfavourable effects associated with antiepileptic drugs and have been related to poor reaction to pharmacological and surgical treatments. Furthermore, people with depression or anxiety have been more likely to suffer from epilepsy than those without depression or anxiety. It is better to consider the treatment of anxiety in these patients. Anxiety disorders in patients with epilepsy can be effectively treated with counselling and medical treatment.

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Epilepsy is a brain disorder that causes people to have recurring seizures. The seizures happen when clusters of nerve cells, or neurons, in the brain send out the wrong signals. Up to 50 or 60% of patients with chronic epilepsy have various mood disorders including depression and anxiety. Although the affective and cognitive effects of epilepsy have long received attention, the anxiety spectrum of psychiatric complications of epilepsy has not been well-studied. Anxiety is a general term for several disorders that cause nervousness, fear, apprehension and worrying. These disorders affect how we feel and behave, and they can manifest real physical symptoms. The goal of this investigation was to review the different views about the relationship between anxiety and epilepsy. We performed a systematic literature search, using PubMed with the following entry: "Epilepsy"[Mesh] AND "Anxiety"[Mesh]. The search resulted in identifying 580 studies. Full texts of articles which met the inclusion criteria and their finding are discussed in this study. Increased recognition of anxiety disorders among patients with epilepsy, offers a potentially rich nexus for theoretical and empiric investigation of the neurocircuitry and psychological mechanisms underlying each phenomenon.

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Anxiety and depression are very common in population and occur in a wide range of clinical states and is very common in epileptic patients. Many recent epidemiological studies have found a high prevalence of depression and anxiety in epileptic patients. These studies found that epileptic patients suffered from depression and anxiety than those without epilepsy. The prevalence of depression or anxiety is higher in drug refractory epilepsy, especially temporal-lobe epilepsy. Depression and anxiety have been associated with increased adverse events in response to anti-epileptic drugs in epileptic patients. Structural abnormalities, monoamine pathways, cerebral glucose metabolism, the hypothalamic pituitary adrenal axis and interleukin-1β all plays a crucial role in the common pathogenesis of these conditions. Studies that have examined depressed patients using high-resolution brain MRI have shown reductions in the volumes of various areas, including the frontal, temporal, limbic regions and hippocampus (the left and right hippocampus in temporal-lobe epilepsy and depression). Findings of reductions in hippocampal volume suggest that depression and epilepsy reflect common structural abnormalities. The symptoms of depressive disorders in epileptic patients can be classified according to their temporal relationship with seizures. The psychiatric and clinical effects of depression and anxiety can impair the quality of life of epileptic patients. Therefore, early detection and management of depression and anxiety are critical for the management of epileptic patients.

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Introduction: Epilepsy has been known as a chronic brain disorder, influences large number of population around the world. Seizures should be treated as soon as possible to avoid the development of chronic epilepsy. Furthermore, there are some complications following surgical resection of epileptic focus and drug treatment. Transcranial magnetic stimulation has been suggested to generate current flow in the brain and could be an alternative to drug treatment or surgery. We study the protective effects of repetitive transcranial magnetic stimulation (rTMS) on seizure attacks and cellular damage in the amygdala in rats. Materials and Methods: In the present study four groups of rats including intact, pentylenetetrazole, rTMS+pentylenetetrazole and rTMS were used to investigate rTMS effects on cellular activity and seizure attacks in a model of epilepsy. The rTMS was applied for a month and then seizures was induced by intraperitoneally injection of pentylenetetrazole and seizure scores were determined. Finally, rats were killed and neuronal injury was evaluated in the amygdala. Results: Seizure scores as well as histological assessment revealed a significant reduction on seizure attacks and the mean number of necrotic cells in the amygdala following rTMS application. Conclusion: This study advocated a protective effect of rTMS on cellular structure in epilepsy. However, safety of rTMS in clinical practice need further investigations.

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Traumatic head injury is the underlying cause of approximately 5% of all persons with epilepsy and is the major cause of epilepsies starting in young adulthood. Penetrating head injury, particularly among soldiers, carries a risk of almost 50% of developing post-traumatic epilepsy (PTE), mostly within 6 months to two years after the trauma. Early seizures (within one week of the trauma) are dependent on the severity of the trauma and do not independently contribute to the risk of developing PTE. The pathophysiology of development of chronic seizures is not fully understood. The process of epileptogenesis and post injury recovery share some characteristics such as neurogenesis and axonal sprouting. Unspecific hippocampal damage as well as hemosiderin remnants from bleedings may play a role. There is no evidence supporting routine use of antiepileptic drugs beyond the first week after trauma for seizure prophylaxis. Treatment after the first seizure beyond 1-2 weeks after the trauma is indicated because the risk of seizure recurrence within 2 years is almost 90%. As of yet, no anticonvulsant has been singled out as being particularly effective in PTE. Seizure remission with medical treatment can be expected in 25%- 40% of the patients. Epilepsy surgery may be an option, but seems to be less effective when compared with other etiologies such as hippocampal sclerosis or benign tumors.

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In the last century, neural stem cells are used in a lot of studies for basic and therapeutic investigations. Several sources are identified for neural stem cells including embryonic, fetal and adult stem cells. Although most of studies have focused in embryonic as well as fetal cells due to their capacity to generate progenies, these cells have some problems such as immunological, availability and ethical concerns. Among adult sources for neural stem cells, two areas in adult mammalian brain including the subventricular zone of lateral wall of lateral ventricle and the subgranular zone of hippocampus are identified as niches with neural stem/progenitor cells (NS/PCs). According to previous studies, other adult mammalian brain regions may have the quiescent cells which generate stem-like cells in vitro. To date, a few researches have addressed the isolation of NS/PCs from adult human amygdala. The aim of the present study was to evaluate the ability of human amygdala tissue to generate neurosheres. The amygdala specimens were obtained from five patients suffering from refractory temporal lobe epilepsy and subjected to amigdalo-hippocampectomy. After removing the pia mater and associated blood vessels, the tissue was dissociated enzymatically. Then, the single cells were cultured in neurosphere medium containing 20 ng/ml Fibroblast growth factor, 20 ng/ml epidermal growth factor, B27 supplement and N2 supplement in non-coated flasks. Growth factors were added twice a week. Additional neurosphere medium was administered once every week. The efficacy and number of spheres and cells were evaluated. Four days after primary culture of amygdala tissue, small free flouting spheres were appeared. The proliferation of the cells slowly continued to day 15 at which passage was done and neurospheres dissociate into single cells. The number of spheres and cells increased after each passage. Here, we showed for the first time in Iran the possibility of isolating proliferating neurospheres from patients with refractory epilepsy during interventional surgery.

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Several sources were introduced for cell therapy after neurotrauma. There are some evidences that quiescent stem cells are located in the various regions of the adult mammalian brain including cortex, hippocampus, amygdala and striatum. But more study is needed to identify the characteristics of these cells. In the present study we investigated the possibility of isolating neural stem cells from adult human amygdala. The amygdala specimens were obtained from five patients suffering from refractory temporal lobe epilepsy and subjected to amygdalo-hippocampectomy. After removing the pia mater and associated blood vessels, the tissue was dissociated enzymatically. Then, the single cells were cultured in neurosphere medium containing 20 ng/ml Fibroblast growth factor, 20 ng/ml epidermal growth factor, B27 supplement and N2 supplement in non-coated flasks. Growth factors were added twice a week. Additional neurosphere medium was administered once every week. To characterize the isolated cells, immunocytochemistry was done against nestin, Sox2, Oct4, GFAP and MAP2. The isolated cells highly expressed neural stem cell markers nestin, Sox2 and Oct4. But there was a few cells expressed mature neuron marker MAP2 and astrocyte marker GFAP. Here, we showed for the first time in Iran the possibility of isolating neural stem-like cells from patients with refrac‌tory epilepsy during interventional surgery.

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In this research, we have computationally investigated a mechanism for antiepileptic drugs (AED) and proposed bumetanide as a possible temporal lobe epilepsy (TLE) treatment. Experimentally it is difficult and devastating to determine the ionic mechanisms of depolarizing currents. It is obvious that chlorine and potassium transients are challenging to isolate pharmacologically and much γ-aminobuytric acid )GABA( signaling occurs in small, difficult to measure, dendritic compartments. So many computational studies have been done to confirm the mechanisms of TLE. Despite widespread acceptance of GABA as the transmitter of inhibition in the central nervous system, in one of the most frequent reported TLE data, GABA plays role of excitatory neurotransmitter. In this computational study we have modeled three hippocampal neurons. We have modeled healthy, patient and bumetanide treated neuron and the compared the firing rate of these three neurons. The computationally based model neuron was morphologically reconstructed from hippocampal pyramidal neuron n123 taken from the published Duke Southhampton neuronal morphology: from the published Duke Southhampton neuronal morphology: http://www.compneuro.org/CDROM/nmorph/index/n123_t.html. The model was modified to include an axon, as described in Poirazi and et al. The neuron contains 183 compartments. Voltage gated ionic currents were modeled as in Poirazi and et al modified by Naomi Lewin et.al. The extracellular space was modeled as a cylindrical shell surrounding each compartment with a volume 15% of the intracellular compartment. The initial intracellular concentrations of Na+, K+, Cl-, Ca2+and HCO3- were based on the intracellular and extracellular concentrations described in Smirnov et al. The concentrations of Na+, K+, Cl- and Ca2+ were allowed to fluctuate in both the intracellular and extracellular compartments, except where specified. The results showed that blocking the Cl- importer Na-K-Cl cotransporter 1 (NKCC1) is significantly reducing firing rate so NKCC1 blockers such as bumethanide are potential anti-epileptic drugs. Due to these computations, we are experimentally testing bumetanide’s effect on animal subjects. In conclusion combined treatment with bumetanide and phenobarbital after status epilepticus (SE), increase inhibition and maximize the anticonvulsant power of the GABA system and might be useful in the treatment of epilepsy patient.

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Traumatic brain injury (TBI) refers to a brain injury caused by an external mechanical force such as an impact to the head, concussive forces, acceleration–deceleration forces, blast injury, and a projectile such as a bullet. Traumatic brain injury is recognized as a critical public health problem worldwide, TBI is accompanied with mortality and morbidity with an occurrence of approximately 200cases per 100,000 people a year. It is also a known major risk factor for focal epilepsy. The incidence of post-traumatic epilepsy (PTE) ranges from 2–50% in different studies, accounting for approximately 20% of symptomatic epilepsies .Seizures may occur immediately following the trauma, though PTE usually develops several months and even years later. While immediate post-traumatic seizures may be successfully treated with antiepileptic drugs, the mechanisms underlying the development of PTE remain unknown with no means for preventing it. The central nervous system is protected by the function of the blood-brain barrier (BBB), which regulates the passage of blood constituents in and out of the brain extracellular space. It seems that an increase in BBB permeability may be associated with the pathogenesis of neurological disorders. However, only recent animal experiments directly showed that primary prolonged opening of the BBB leads to the development of delayed, long-lasting epileptiform activity. Furthermore, it has been suggested that the most common serum protein, albumin may underlie astrocytic activation and dysfunction, further leading to neuronal hyper synchrony and accumulated neuronal loss. On the other hand previous clinical studies showed that altered permeability is observed in neurological patients.

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Post-traumatic epileptic seizure is a common complication of brain trauma including military injuries. We present clinical characteristics and correlates of post-traumatic epilepsy in 163 head-injured veterans suffering from intractable epilepsy due to blunt or penetrating head injuries sustained during the Iraq-Iran war. The medical records of 163 war veterans who were admitted by the Epilepsy Department of the Shefa Neuroscience Center between 2005 and 2009 were retrospectively reviewed. The mean follow-up period after developing epilepsy was 17.2 years. The time interval between the trauma and the first seizure was shorter and the seizure frequency was higher in epileptic patients suffering from penetrating head trauma. There was no difference in seizure type between epileptic patients traumatised by blunt or penetrating injury. Patients with seizure frequency of more than 30 per month mostly had simple partial seizure. Frontal and parietal semiologies were observed more frequently in patients with penetrating trauma, whereas patients with blunt trauma showed a higher temporal semiology. The most common brain lesion observed by CT scan was encephalomalacia followed by porencephaly and focal atrophy. There was no association between intracerebral retained fragments and different characteristic features of epilepsy. Patients with military brain injury carry a high risk of intractable post-traumatic epilepsy decades after their injury, and thus require a long-term medical follow-up.

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Epilepsy is one of the most prevalent serious neurologic conditions, affect 1 % of the population worldwide. People with epilepsy may feel it's safe to drive when their seizures seem to be under control, but patients with epilepsy were seven times more likely to have a driving accident leading to emergency room care than those without epilepsy. People with seizures had 2.3 times the rate of fatal driver crashes as people with cardiovascular disease or high blood pressure and 4.6 times the rate for patients with diabetes. From results of a survey of 72 epileptic car drivers who had a mean driving history of 8.6 years, 18 (25%) had experienced one or more automobile accidents ascribed to a seizure while driving, with the total number of accidents of the surveyed group amounting to 35. All the drivers were known to have partial epilepsy, 13 of them having temporal lobe epilepsy. Most accidents caused damage to only the driver's car and/or mild physical injury and fifty-four percent of the accidents were not reported to the police, and many that were reported were ascribed to driving while asleep, to careless driving or to similar behavior.

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Introduction: A typical absence epilepsy is a type of nonconvulsive and generalized epilepsy. The main feature of these attacks is a sudden brief impairment of consciousness. The disturbances in thalamocortical loop play an important role in pathogenesis of absence seizures. However, it is not clear that which part of this network triggers the seizure. This study was aimed to investigate the role of latrodorsal (LD) thalamic neurons during spike and wave discharges (SWDs) in WAG/Rij rats, as the most valid animal model of absence epilepsy. Materials and Methods: Single unit activities in the LD thalamic nucleus and electrocorticogram of somatosensory cortex were simultaneously recorded in six-month-old WAG/Rij rats. Results: During SWDs, unit activity in the LD thalamic nucleus showed burst-like discharges, which were started before the peak component of SWDs. In SWD-free periods, burst like activity in the LD was reduced. Conclusion: Our findings suggest that the burst firing of LD may stimulate the neocortex to exhibit SWDs. It can be concluded that inhibition of burst firing of LD neurons may reduce the frequency of SWDs.