javad mirnajafi zadeh

Deep brain stimulation (DBS) is a new therapeutic method for the treatment of neurological disorders such as epilepsy. However, the precise procedure underlying the anticonvulsant action of high-frequency stimulation (HFS) has remained unclear. This study explores the effect of HFS applied to the olfactory bulb (OB) on seizure-induced changes in spontaneous excitatory postsynaptic currents (sEPSCs) in kindling animals.

Male rats underwent a kindling procedure involving semi-rapid electrical stimulation (6 stimulations per day) of the hippocampal CA1 region. Fully kindled animals received HFS (at 130 Hz) at 5 min, 6 h, 24 h, and 30 h after the last kindling stimulation (kindled+HFS group). Subsequently, the impact of HFS on EPSCs was evaluated in CA1 pyramidal neurons of hippocampal slices from kindled subjects using the whole cell patch clamp technique. 

In kindling animals, sEPSC amplitude increased (P<0.001), while the sEPSC inter-event interval decreased compared to the control group (P<0.05). Applying HFS in the OB of fully kindled animals resulted in a reduction in sEPSCs amplitude and an increase in the inter-event interval of sEPSCs. No significant differences between kindling and control groups were observed in membrane potential and input resistance. Notably, the application of HFS in kindling animals restored the observed changes, so no significant difference was observed in the measured parameters between the kindled+HFS and control groups.

These findings suggest that the OB may be a viable target for DBS in epilepsy treatment. HFS application may mitigate a seizure-induced increase in sEPSCs occurrence.

More than fifty percent of drug abusers start their substance abuse in adolescence. Chronic exposure to morphine, particularly during this developmental stage, may lead to long-lasting effects that can be transmitted to subsequent generation. The present study investigated the impact of paternal morphine exposure during adolescence on anxiety-like behavior in their male offspring during adulthood.

Male Wistar rats were exposed to increasing doses of morphine (5–25 mg/kg, s.c.) or saline for 10 days at postnatal days (PND) 30–39 during adolescence. Following a 20-day drug-free period, the treated male rats were mated with naïve females. Adult male offspring (PND 60–70) were assessed for anxiety-like behavior using the elevated zero maze test. The experiments were conducted on two groups of offspring. One group had a male parent that received saline, while the other group had a male parent that received morphine. The number of rats in each group was 14.

Offspring whose male parent was exposed to morphine exhibited reduced anxiety-like behavior compared to the control group. The findings of this study suggest that paternal exposure to morphine during adolescence may influence anxiety-like behaviors in male offspring and lead to reduced levels of anxiety in adulthood.

These results indicate that early substance use may have complex intergenerational effects and underscore the importance of understanding the long-term consequences of drug exposure during adolescence. Further research should focus on investigating the underlying mechanisms that induce behavioral changes and their potential impacts on mental health across different generations.

The differences among dorsal and ventral hippocampal neural circuits affect synaptic plasticity. In this study, we aim to compare the occurrence of short-term plasticity in the field excitatory postsynaptic potential (fEPSP) in dorsal and ventral hippocampal CA1 areas following kindled seizures.

Animals (male C57 B6/J mice, 12 weeks of age) were kindled by intraperitoneal injections of pentylenetetrazole (PTZ), and fEPSPs were recorded from dorsal and ventral hippocampal slices. Short-term plasticity was evaluated by measuring fEPSP-slope and fEPSP-area following paired-pulse stimulation delivered at three inter-pulse intervals (20, 80, and 160 ms).

In control slices, the fEPSP-slope was greater in the ventral hippocampus compared to the dorsal hippocampus, but there was no difference in the fEPSP-area between the two regions. In hippocampal slices, the fEPSP-slope was similar in the dorsal and ventral regions, but the fEPSP-area was greater in the ventral region compared to the dorsal region. In addition, the fEPSP-area was greater in the kindled group than in the control group only in the ventral hippocampus. PTZ-induced kindled slices showed impaired short-term facilitation, and the paired-pulse index decreased only in the dorsal hippocampus. Kindling had no significant effect on the paired-pulse ratio in the ventral hippocampus.

The seizure occurrence affects the neural activity of the hippocampus in a region-dependent manner. Although kindling increases the fEPSP area in the ventral hippocampus of mice, kindling-induced changes in short-term synaptic plasticity are significant only in the dorsal hippocampus. The difference in the responses of dorsal and ventral poles should be considered in future studies.

Epilepsy is a chronic neurological disorder that lacks an effective treatment, and most patients do not respond to existing medications. It is due to the lack of a molecular mechanism of epilepsy and the incomplete understanding of proteins that are involved that epilepsy is largely unknown. It is therefore important to identify and control the epileptic process so that relevant and effective drug treatments can be administered. This study used the electrical kindling method and the proteomics shotgun technique to analyze the proteomes of rats during epileptogenesis. From the analysis of system biology data, it was determined that the cAMP signaling pathway is involved in epilepsy, as well as changes in the expression of proteins that are upstream and downstream of this secondary messenger in the stages of electrical kindling was observed. There was a significant decrease in expression of somatostatin neuropeptide from upstream proteins and an increase in expression of phospholipase D2 and AMPA glutamate receptor type 2 from downstream proteins during epilepsy. Taking advantage of these data, we can consider a new method to identify the mechanism of epilepsy and introduce new drug targets by identifying changes in the expression of cAMP signaling pathway proteins and their roles in the epilepsy process.

Deep brain stimulation (DBS) stands as an alternative treatment for drug-resistant temporal lobe epilepsies. In this study, we investigated the effects of both low- and high-frequency stimulation (LFS and HFS) of the olfactory bulb on locomotor activity and preferences for spending time in the central or border regions. Rats underwent a kindling procedure involving semi-rapid electrical stimulation (6 stimulations per day) of the hippocampal CA1 region. Fully kindled animals received LFS (1 Hz) or HFS (130 Hz) at four time points: 5 min, 6 h, 24 h, and 30 h after the last kindling stimulation. Subsequently, rats were placed in the open field chamber and allowed free, uninterrupted movement within the respective quadrant of the maze for a single 10-minute period. During this time, tracking software recorded movement, and locomotor activity as well as preferences for spending time in the central or border regions were evaluated. Overall, applying DBS in the olfactory bulb at both low and high frequencies decreased exploration time in the center and increased exploration time in the border for the rats. Furthermore, a higher intensity of HFS was more effective than a lower intensity of HFS in reducing anxiety or altering locomotor behavior. According to the results of the present study it may be suggested that applying DBS affects some aspects of the animals’ activity and therefore, the activity monitoring tests have to be done following DBS application.

Application of Low-frequency stimulation (LFS), is accompanied with a decrease in hippocampal kindled-seizure induced changes rats and prevents propagation of seizure. The purpose of this study is to investigate the role of the endocannabinoids receptors CB2 in the inhibitory effects of LFS on perforant path kindling- arose seizures. Rats Animals were kindled through electrical stimulation of perforant path and recorded responses in the dentate gyrus. Animals included of four groups kindled, Kindled+LFS (KLFS), LFS and control. Semi- rapid kindling procedure was used to induce seizures in animals. In group of KLFS, LFS (0.1 ms pulse duration at 1 Hz, 800 pulses) was applied five min after termination of kindling stimulations. Obtained results showed that LFS application in the LFS-treated group (KLFS) had significantly reduced seizures parameters. However, on basis immunohistochemical findings, no significant change in level of expression CB2 receptors was observed following LFS stimulations in the gyrus dentate of the KLFS group. It is suggested that CB2 receptors may have no role in anticonvulsant effect of the LFS.

The mechanisms behind seizure suppression by deep brain stimulation (DBS) are not fully revealed, and the most optimal stimulus regimens and anatomical targets are yet to be determined. We investigated the modulatory effect of low-frequency DBS (L-DBS) in the ventral tegmental area (VTA) on neuronal activity in downstream and upstream brain areas in chemically kindled mice by assessing c-Fos immunoreactivity.

In this experimental study, 4-6 weeks old BL/6 male mice underwent stereotaxic implantation of a unilateral stimulating electrode in the VTA followed by pentylenetetrazole (PTZ) administration every other day until they showed stage 4 or 5 seizures following 3 consecutive PTZ injections. Animals were divided into control, sham-implanted, kindled, kindled-implanted, L-DBS, and kindled+L-DBS groups. In the L-DBS and kindled+L-DBS groups, four trains of L-DBS were delivered 5 min after the last PTZ injection. 48 hours after the last L-DBS, mice were transcardially perfused, and the brain was processed to evaluate c-Fos expression by immunohistochemistry.

L-DBS in the VTA significantly decreased the c-Fos expressing cell numbers in several brain areas including the hippocampus, entorhinal cortex, VTA, substantia nigra pars compacta, and dorsal raphe nucleus but not in the amygdala and CA3 area of the ventral hippocampus compared to the sham group.

These data suggest that the possible anticonvulsant mechanism of DBS in VTA can be through restoring the seizure-induced cellular hyperactivity to normal.

In epilepsy as a chronic neurological disease, there are significant alterations in the brain network which results in abnormal brain activity. Understanding the exact changes in brain rhythms may help the investigators to find the brain networks activity in health and disease more precisely. In this article, at first we reviewed the findings from recent animal and clinical studies showing that brain rhythms are affected in the epileptic brain. Then, some documents demonstrating the compensative effect of DBS on these oscillations will be discussed. In this article we reviewed the studies in field of epilepsy and brain rhythms. For this purpose we searched the duciments by scientific serach engeens including PubMed, ScienceDirect and Google Scholar. The electrophysiological studies have indicated significant changes in delta (1–4 Hz), theta (4-7 Hz), alpha (8-12 Hz), beta (13–30 Hz), and gamma (30–80 Hz) oscilations in the epileptic brain. Recently, deep brain stimulation (DBS) has been suggested as a potential and efficient treatment for pharmacoresistant epileptic seizures. The exact mechanism of DBS action is unclear, but some studies demonstrate that one of its probable mechanisms is modulating neural network activity. It seems that the probable compensative alteration in brain rhythms may be considered as a mechanism of DBS anticonvulsant action.

Drug addiction is a serious medical and social problem around the world. More than 50 percent of substance use cases were initiated between the ages of 15-19. Adolescence is the period between childhood and adulthood. In rats, the period between postnatal days (PND) 28 and 42 is considered the early-mid adolescence (12–17 years in human), whereas the later interval (PND 43–55) may model the late adolescence/emerging adulthood period (18–25 years in humans). Adolescence is a critical time of brain development and maturation. Many researchers have shown that certain epigenetic changes can transfer from parents to offspring through DNA methylation, histone acetylation and different types of small noncoding regulatory RNAs. There is compelling evidence for the effect of parental drug abuse such as opioid, cocaine, nicotine, cannabinoid and alcohol on the offspring. In this report, we will study the effects of Adolescent drug abuse on behavior and cognitive aspects of offspring.

Glioblastoma multiforme is the most malignant and invasive primary brain tumor in adults. The disease has a poor prognosis with a survival rate of 14-16 months post diagnosis. Depending on the tumor location in the brain, a wide range of signs and symptoms may appear in the patient. One of the most common of which is recurrent hard to control seizures. Despite the high prevalence of tumor-induced seizures, the mechanisms involved in its occurrence are yet to be fully identified. However, it has been shown that glutamate and GABA are probably the major contributing factors. Increasing extracellular glutamate levels due to changes in the expression of ion transporters and the conversion of GABA to a stimulatory mediator are some of the mechanisms involved in the development of these seizures. In addition, factors such as the complex pathophysiology of the disease, its associated-seizures, drug interactions, resistance to treatment and tumor recurrence have made glioblastoma management a major challenge. In this article, the common clinical symptoms of this disease and in particular tumor-associated seizures are reviewed. The mechanisms thought to be responsible for the development of the tumor-induced seizures are then discussed.

Alzheimerchr('39')s disease is the most common cause of dementia in middle age and aging. It is the third leading cause of death among the elderly. Alzheimerchr('39')s disease is a neurodegenerative disorder, characterized by attention deficits, memory and learning impairment. Many researches try to find new alternative treatment options for Alzheimerchr('39')s disease. Deep brain stimulation (DBS) is one of the new therapies for treating this disease. Early studies have shown that applying DBS in the hippocampus, meynert nucleus, fornix, and entorhinal cortex of patients as well as experimental Alzheimer-like models in animals can improve learning abnormalities and increase the volume of the hippocampus. The mechanisms responsible for this effect are still unknown, but maybe DBS effect through changes in neurotransmitters and neuromodulators release, thereby regulates the neuronal activities. In this article, we first review the common drug treatments for Alzheimerchr('39')s disease and their complications, and then review the effect of DBS on the Alzheimerchr('39')s patient and the animal model of Alzheimerchr('39')s, and finally discuss the possible mechanisms involved in these therapeutic effects and changes in neurotransmitters.

The neuropeptide orexin is synthetized in the lateral hypothalamus (LH) and is involved in naloxone-precipitated morphine withdrawal syndrome via orexin type 1 receptors (OX1R). Locus coeruleus (LC) is a sensitive site for the expression of somatic aspects of morphine withdrawal. The orexinergic and GABA-A-ergic systems are involved in morphine withdrawal syndrome. In this study, the effect of OX1R at the LC neurones on GABA-A-ergic inhibitory system activity in morphine withdrawal syndrome was investigated.

Male Wistar rats (14-21 days) were made dependent on morphine (20 mg/kg, i.p., for 7 days). Then the effect of orexin-A on spontaneous and evoked inhibitory post synaptic currents in LC neurons using whole-cell patch clamp recordings was assessed.

The findings of this study indicated that orexin-A through OX1R in the presence of naloxone may induce an inhibitory effect on GABAergic system in the LC neurons. It seems that the orexin-A administration decreased the eIPSCs amplitude in LC neurons. OrexinA decreased spontaneous sIPSCs frequency of LC neurons, but did not change the sIPSCs amplitude in the presence of naloxone.

These findings implicated evidence that orexin-A via OX1R may participate in expression of naloxone-precipitated morphine withdrawal syndrome through decreasing of GABAA receptor activity.

In this study, the role of A1 adenosine receptors in improving the effect of Low-Frequency Electrical Stimulation (LFS) on seizure-induced hyperexcitability of hippocampal CA1 pyramidal neurons was investigated.

A semi-rapid hippocampal kindling model was used to induce seizures in male Wistar rats. Examination of the electrophysiological properties of CA1 pyramidal neurons of the hippocampus using whole-cell patch-clamp recording 48 h after the last kindling stimulation revealed that the application of LFS as two packages of stimulations at a time interval of 6 h for two consecutive days could significantly restore the excitability CA1 pyramidal neurons evidenced by a decreased in the of the number of evoked action potentials and enhancement of amplitude, maximum rise slope and decay slope of the first evoked action potential, rheobase, utilization time, adaptation index, first-spike latency, and post-AHP amplitude. Selective locked of A1 receptors by the administration of 8-Cyclopentyl-1,3-dimethylxanthine (1 μM, 1 μl, i.c.v.) before applying each LFS package, significantly reduced LFS effectiveness in recovering these parameters. 

On the other hand, selective activation of A1 receptors by an injection of N6-cyclohexyladenosine (10 μM, 1 μl, i.c.v.), instead of LFS application, could imitate LFS function in improving these parameters. 

It is suggested that LFS exerts its efficacy on reducing the neuronal excitability, partially by activating the adenosine system and activating its A1 receptors.

Cell therapy has provided clinical applications to the treatment of motor neuron diseases. The current obstacle in stem cell therapy is to direct differentiation of stem cells into neurons in the neurodegenerative disorders. Biomaterial scaffolds can improve cell differentiation and are widely used in translational medicine and tissue engineering. The aim of this study was to compare the efficiency of two-dimensional with a three-dimensional culture system in their ability to generate functional motor neuron-like cells from adipose-derived stem cells.

We compared motor neuron-like cells derived from rat adipose tissue in differentiation, adhesion, proliferation, and functional properties on two-dimensional with three-dimensional culture systems. Neural differentiation was analyzed by immunocytochemistry for immature (Islet1) and mature (HB9, ChAT, and synaptophysin) motor neuron markers.

Our results indicated that the three-dimensional environment exhibited an increase in the number of Islet1. In contrast, two-dimensional culture system resulted in more homeobox gene (HB9), Choline Acetyltransferase (ChAT), and synaptophysin positive cells. The results of this investigation showed that proliferation and adhesion of motor neuron-like cells significantly increased in three-dimensional compared with two-dimensional environments.

The findings of this study suggested that three-dimension may create a proliferative niche for motor neuron-like cells. Overall, this study strengthens the idea that three-dimensional culture may mimic neural stem cell environment for neural tissue regeneration.

Electrical Kindling is one of the most popular epileptic model techniques that cause seizures such as temporal lobe epilepsy. So far, various therapies have been used to treatment of epilepsy. Among these treatments, low-frequency stimulation (LFS) has been widely considered for improving effect on drug-resistant epilepsy, but its mechanism is not well understood. Since calcium entering to the cytoplasm and increasing its concentration is one of the reasons for seizure, metabotropic glutamate receptor (mGluR1), dopamine receptor (D1) and ADPR cyclase (CD38), which increased calcium in the cytoplasm from different pathways, were selected. With this aim that by examining the change in the expression of these genes, we help to clarify the LFS improvement effect.  In this study, the hippocampus of rats was used and the changes in genes expression were investigated using real-time PCR technique. The results showed that the expression of all selected genes  increased significantly after kindling and then after the LFS the expression of all was returned to sham value. Hence, one of the ways in which LFS interferes may be related to the pathway for calcium entering to the cytoplasm.

There are evidences that olfactory bulb (OB) activity during nasal breathing continuously generates respiration-coupled oscillations in widespread neocortical and subcortical regions. Nasal breathing creates oscillations associated with the breathing cycle in the olfactory bulb, which are transmitted to primary areas of the olfactory system such as the piriform cortex. Recently these respiratory related oscillations have been reported in the medial prefrontal cortex (mPFC) region too. However, it has not been investigated that whether applying nasal airflow in the absence of nasal breathing may cause these oscillations in the mPFC region or not. In this study we applied airflow in nostrils rats and recorded OB and mPFC local field potential (LFP). We observed that applying nasal airflow can stimulate mPFC and this method can introduce as a non-invasive method to stimulate the mPFC region and increase the electrical activity of this area.

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.

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.

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.

It may be suggested that power is a suitable parameter for online analysis of LFP in order to detect the spontaneous seizures correctly.

Synaptic plasticity has been suggested as the primary physiological mechanism underlying memory formation. Many experimental approaches have been used to investigate whether the mechanisms underlying Long-Term Potentiation (LTP) are activated during learning. Nevertheless, little evidence states that hippocampal-dependent learning triggers synaptic plasticity. In this study, we investigated if learning and memory in the Barnes maze test are accompanied by the occurrence of LTP in Schaffer collateral to CA1 synapses in freely moving rats.

The rats were implanted with a recording electrode in stratum radiatum and stimulating electrodes in Schaffer collaterals of the CA1 region in the dorsal hippocampus of the right hemisphere. Following the recovery period of at least 10 days, field potentials were recorded in freely moving animals before and after training them in Barnes maze as a hippocampal-dependent spatial learning and memory test. The slope of extracellular field Excitatory Postsynaptic Potentials (fEPSPs) was measured before and after the Barnes maze test.

The results showed that the fEPSP slope did not change after learning and memory in the Barnes maze test, and this spatial learning did not result in a change in synaptic potentiation in the CA1 region of the hippocampus.

Spatial learning and memory in the Barnes maze test are not accompanied by LTP induction in Schaffer collateral-CA1 synapses.

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.
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.
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.
Increasing the numbers of LFS pulses can magnify its inhibitory effects on EA-induced changes in AP features.

The locus coeruleus (LC) contains large clusters of noradrenergic neurons which project widely throughout the central nervous system including hypothalamus. The LC is involved in cognitive processes, including attention, learning, memory and drug addiction. Orexin neuropeptides excite the noradrenergic LC neurons; however, its effects on inhibitory synaptic transmission to the LC neurons are unknown.
Here, we investigated the effect of orexin-A (100 nM) on sIPSCs in LC neurons. We used whole-cell patch clamp recording in rat horizontal slices containing the LC nucleus.
Our electrophysiological data indicate that orexin-A application only decreased sIPSCs frequency of LC neurons that was blocked by SB-334867, selective orexin type-1 receptors.
In this study, our findings suggest that orexin-A depresses sIPSCs frequency through orexin type-1 receptors. It can be deduced that these changes in inhibitory synaptic transmission may be elicited by prestsynaptic mechanism. These results provide in vitro evidence for a critical role of orexin signaling in LC neurons.

The life quality of patients with epileptic seizures is highly affected by cognitive deficits. Low Frequency Stimulation (LFS) is a novel approach for the treatment of pharmacoresistant epilepsy. The main goal of this research is investigating the possible effect of LFS on seizure-induced cognitive dysfunction.
To this end, the kindled animal were prepared via CA1 electrical stimulation in a semi-rapid way (12 stimulations/day). A group of animals were stimulated with LFS, 4 times at 30 s, 6 h, 24 h, and 30 h after the last kindling stimulation. Applied LFS was administered in 4 packages every 5 minutes. The packages were designed with 200 monophasic 200 monophasic square wave pulses of 0.1 ms duration at 1 Hz. The passive-avoidance test was conducted on all animals in order to measure the learning and memory behavior.
Hippocampal kindled rats showed deficits in learning and memory when passive avoidance test was performed. Application of LFS reversed the impairment in learning and memory behavior in kindled rats. At the same time, LFS markedly diminished kindling-induced neuronal loss and atrophy in the hippocampus.
LFS may have some protection against seizure-induced cognitive damage in kindled rats.

Epilepsy is accompanied with a strong change in neuronal activity not only in excitatory (glutamatergic) and inhibitory (GABAergic) neurotransmission, but also in neuromodulatory agents. Dopaminergic system, as an important neuromodulatory system of the brain, has significant effect on neuronal excitability. In addition, this system undergoes many changes in epileptic brain. Understanding the effects of dopaminergic system in neuronal activities in epileptic brain and knowing the seizure-induced changes in dopaminergic system can shed light into finding the mechanisms involved in epileptogenesis and can help us in finding new treatments for epilepsy. In this review we briefly introduce dopaminergic system and its changes in brain areas which have role in epilepsy. Then, we will focus on the evidences showing the relationship between epilepsy and dopaminergic system.

In the present work sedative and hypnotic effects of aqueous extract of Aloe vera in rats have been investigated. In order to evaluate the overall hypnotic effects of the Aloe vera extract, open field and loss of righting reflex tests were primarily used. The sedative and hypnotic effects of the extract were then confirmed by detection of remarkable raise in the total sleeping time through analysis of electroencephalographic (EEG) recordings of animals. Analysis of the EEG recordings showed that there is concomitant change in Rapid Eye Movement (REM) and None Rapid Eye Movement (NREM) sleep in parallel with the prolonged total sleeping time. Results of the current research show that the extract has sedative-hypnotic effects on both functional and electrical activities of the brain.

Hippocampal insults have been observed in multiple sclerosis (MS) patients. Fibroblast growth factor-2 (FGF2) induces neurogenesis in the hippocampus and enhances the proliferation, migration and differentiation of oligodendrocyte progenitor cells (OPCs). In the current study, we have investigated the effect of FGF2 on the processes of gliotoxin induced demyelination and subsequent remyelination in the hippocampus. In this experimental study adult male Sprague-Dawley rats received either saline or lysolecithin (LPC) injections to the right hippocampi. Animals received intraperitoneal (i.p.) injections of FGF2 (5 ng/g) on days 0, 5, 12 and 26 post-LPC. Expressions of myelin basic protein (Mbp) as a marker of myelination, Olig2 as a marker of OPC proliferation, Nestin as a marker of neural progenitor cells, and glial fibrillary acidic protein (Gfap) as a marker of reactive astrocytes were investigated in the right hippocampi by reverse transcriptase-polymerase chain reaction (RT-PCR). There was reduced Mbp expression at seven days after LPC injection, increased expressions of Olig2 and Nestin, and the level of Gfap did not change. FGF2 treatment reversed the expression level of Mbp to the control, significantly enhanced the levels of Olig2 and Nestin, but did not change the level of Gfap. At day-28 post- LPC, the expression level of Mbp was higher than the control in LPC-treated animals that received FGF2. The levels of Olig2, Nestin and Gfap were at the control level in the non-treated LPC group but significantly higher in the FGF2-t reated LPC group. FGF2 enhanced hippocampal myelination and potentiated the recruitment of OPCs and neural stem cells (NSCs) to the lesion area. Long-term application of FGF2 might also enhance astrogliosis in the lesion site.

Considering the antiepileptogenic effects of repeated transcranial magnetic stimulation (rTMS), the effect of rTMS applied during amygdala kindling on spontaneous activity of hippocampal CA1 pyramidal neurons was investigated. A tripolar electrode was inserted in basolateral amygdala of Male Wistar rats. After a recovery period, animals received daily kindling stimulations until they reached stage 5 seizure. In one group of animals, rTMS at frequency of 1 Hz were applied to hippocampus once daily at 5 min after termination of kindling stimulations. 24 h after the last kindling stimulation, spontaneous activity of CA1 pyramidal neurons of the hippocampus was investigated using whole cell patch clamp technique. Kindling-induced seizures resulted in increment of spontaneous activity of hippocampal CA1 neurons, but application of rTMS during amygdala kindling prevented it. Moreover, rTMS administration inhibited the kindling-induced enhancement of afterdepolarization (ADP) amplitude and action potential duration. Results of this study suggest that rTMS exerts its anticonvulsant effect, in part, through preventing the amygdala kindling-induced increase in spontaneous activity and excitability of hippocampal CA1 pyramidal neurons.