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Showing 19 results for Kindling

Mirnajafizadeh, Pourgholami, Fathollahi, Behzadi,
Volume 2, Issue 2 (11-1998)

  In this study, the effect of an experimentally increased excitability in hippocampal neurons, via hippocampal kindling, on amygdala kindling rate was investigated in rats. Animals were divided into 4 groups. In all groups, except group 2, tripolar electrodes were implanted in the amygdala and CAI region of the dorsal hippocampus. Group 2 animals were only implanted with tripolar electrodes in the amygdala. In group 1, the rats were kindled one week after surgery, first from the hippocampus, then by amygdala stimulation the next day. In groups 2 and 3, rats were kindled one week after surgery from the amygdala. Group 4 animals had a recovery period of one week plus 32 days, which was the mean of the hippocampal kindling rate in group 1, and then they were kindled from the amygdala. In group 1, the amygdala kindling rate (n number of stimulation trials that must be administered before the stage 5 motor convulsion is triggered) was significantly facilitated and seizure at day n/2 during amygdala kindling was significantly increased. There was also a significant positive correlation between hippocampal and amygdala kindling rates. Results obtained in the present study show that an increase in hippocampal excitability in group 1 could facilitate kindling from the amygdala. Thus it may be suggested that the hippocampus has an important role in the development and propagation of seizures from the amygdala.


Mehdi Saberi, Mohamamd Hossein Pourgholami, Masoumeh Jorjani,
Volume 4, Issue 1 (4-2000)

It has been proved that kindling model of amygdala is sensitive to estradiol because the latter accelerates the overall rate of kindling. However the effect of estrogen on the seizure process has not been investigated. In this study fully kindled male rats were treated with different doses (10, 30, and 50 µg/kg, i.p.) of estradiol benzoate (EB) daily and such kindling parameters as seizure stage (SS), after-discharge duration (ADD) and stage 5 duration (S5D) were recorded 15 and 180 min and every 24 h following EB injection for a period of 96 h. While EB at a dose of 10 µg/kg failed to produce a significant effect, but its administration at doses of 30 and 50 µg/kg induced a triphasic effect on seizure parameters. In this regard an initial rapid increment of ADD (after 15 min) was followed by a significant decrease of all parameters after 48 h and then a significant increase in S5D after 96 h was observed. In addition, pretreatment with tamoxifen citrate (TAM) at a dose of 3 mg/kg inhibited the effects of EB (30 µg/kg) for 72 h and pretreatment with TAM at a dose of 10 mg/kg blocked only the inhibitory phase of EB effects after 48 h. Also treatment with the same dose of TAM alone induced a profile similar to EB treatment. These results may suggest that estradiol treatment both increases and decreases kindling parameters in a time- and dose-dependent manner in male rats. These effects probably manifest themselves in genomic and non-genomic forms. Moreover the tamoxifen effects alone could be attributed to its partial agonistic activity on the estrogen receptors.
Mohamamd Reza Palizvan, Yaghoub Fathollahi,
Volume 4, Issue 1 (4-2000)

Epilepsy is one of the common disorders in human community. Clinical observations have shown that epileptic patients have often difficulty in learning and memory. Kindling is a laboratory model for studying epilepsy and its complications. This experiment was designed to study the effect of chemical kindling on Schaffer collateral-CA1 pyramidal cell synaptic transmission using pentylenetetrazole in urethane-anesthetized rats. Experiments were carried out on the hippocampal CA1 region from control and kindled rats at two periods post-kindling, i.e. 48-144 h (early phase) and 30-33 day (long-lasting phase). Population spike (PS) was recorded at stratum pyramidale following stimulation of the stratum fibers. The results showed that 48-144 h after kindling, the slope of population excitatory post-synaptic potential (pEPSP), the PS amplitude and spike latency in CA1 region of kindled rats were not significantly different than that of control. In contrast, 30 to 33 days after kindling, the amplitude of PS was significantly greater than that of control (p<0.01). These results suggest that chemical kindling entails long lasting changes in the function of CA1 that appear as enhanced excitability after one month
Azam Amini Komijani, Seyed Javad Mirnajafizadeh, Yagoob Fathollahi, Akbar Anayi Godari, Mohammad Mohammadzadeh,
Volume 7, Issue 2 (10-2003)

The effects of intraperitoneal injection of N6-cyclohexyladenosine (CHA, a selective adenosine A1 receptor agonist) and 8-cyclopenthyle-I-3-dimethylexanthine (CPT, a selective adenosine A1 receptor antagonist) on entorhinal cortex-kindled seizures were investigated. Fully entorhinal cortex-kindled rats received normal saline (control), CHA (0.06, 0.12 and 0.25 mg/kg) or CPT (0.06 and 0.12 mg/kg) and 15 min later were stimulated at AD threshold. Obtained data showed that intraperitoneal administration of CHA (0.12 and 0.25 mg/kg) reduced entorhinal cortex afterdischarge duration (ADD), duration of stage 5 of the seizure (S5D) and seizure duration (SD) at 15 min post-drug injection. The latency for stage 4 of the seizure (S4L) also increased at these doses. At the dose of 0.06 mg/kg, CHA only reduced S5D. Intraperitoneal injection of CPT increased ADD only at 0.12 mg/kg, but not at 0.06 mg/kg. Pretreatment of animals with CPT (0.06 mg/kg), 5 min before CHA (0.12 mg/kg) blocked the anticonvulsant effects of CHA. Obtained results may indicate that activity of adenosine A1 receptors reduces the severity of entorhinal cortex-kindled seizures.

Volume 10, Issue 0 (9-2006)

Parviz Ghorbani Moghadam, Mohammad Mohammad-Zadeh,, Javad Mirnajafi-Zadeh, Yaghub Fathollahi,
Volume 10, Issue 3 (11-2006)

Introduction: Electrical low-frequency stimulation (LFS) has antiepileptic effect, but the role of different stimulation parameters on this effect has not been determined. In this study the effect of different LFS parameters (intensity, pulse duration and train duration) on piriform-cortex kindled seizures was investigated. Methods: Seizure was produced in animals using kindling model of epilepsy. Then, the effect of LFS on seizure severity was investigated. Results: Different patterns of LFS (1 Hz) applied immediately before kindling stimulation in fully kindled animals, had no significant effect on seizure parameters. In the second experiment, effect of LFS (1 Hz) on inter-seizure interval was investigated. Data showed that daily stimulation of animals for 15 min with LFS for one week after the last kindling stimulation reduced significantly stage 5 seizure duration. Application of the same LFS protocols for three days and two weeks had no significant effect on seizure parameters. In the third experiment, effect of LFS (1 Hz) on kindling rate was investigated. Results showed that when LFS was delivered daily after each kindling stimulation it could decrease afterdischarge duration in various days during kindling and delayed the appearance of seizure stages 1 and 2 significantly. Conclusion: It may be concluded that LFS has antiepileptic effects on kindling acquisition and inter-seizure interval in kindled animals and that the characteristics of LFS protocol (intensity, pulse duration and train duration) have an essential role on these effects.
Mehdi Sadegh, Javad Mirnajafi-Zadeh, Mohammad Javan, Yaghoub Fathollahi, Mohammad Mohammad-Zadeh, Ali Jahanshahi, Zahra Deljo,
Volume 11, Issue 1 (4-2007)

Introduction: Low-frequency stimulation (LFS) has a delaying effect on kindled seizures acquisition. In the present study we examined the role of galanin receptors in the inhibitory effects of LFS on kindled seizures induced by electrical stimulation of perforant path. Methods: Animals were stimulated daily at the AD threshold intensity with a rapid kindling procedure. LFS was applied immediately after cessation of each kindling stimulation. M35 (0.5 and 1.0 nM per site), a nonselective galanin receptor antagonist, was microinjected daily into the dentate gyrus before the beginning of stimulation protocol and behavioral seizure stages and afterdischarge durations were recorded. Results: LFS application had a suppressive effect on the kindling rate. It significantly increased the number of stimulations needed to reach seizure stages 3, 4 and 5. LFS also decreased the cumulative afterdischarge duration during the days of stimulation. Intra-dentate gyrus microinjection of M35 reduced the inhibitory effect of LFS on kindling rate, significantly. Conclusion: These data indicate that galanin receptors may have a role in mediating part of the inhibitory effects of LFS on perforant path kindled seizures.
Mohammad Mohammad-Zadeh, Javad Mirnajafi-Zadeh, Yaghoub Fathollahi, Mohammad Javan, Parviz Ghorbani,
Volume 11, Issue 2 (8-2007)

Introduction: Previous studies have been shown that low frequency stimulation (LFS) has an inhibitory effect on kindling acquisition. However, the mechanism of this effect has not been completely determined. In the present study, the effect of LFS of the perforant path on seizures induced by rapid perforant path kindling was investigated. Methods: Animals were kindled by electrical stimulation of perforant path. One group of animals (n=6) received LFS (0.1 ms pulses at 1 Hz, 200 pulse, and 50-150 µA) after termination of each kindling stimulations. In control groups, animals received only kindling stimulations (n=8) or LFS (n=4). Basal field potential recording and paired pulse stimulations were done before kindling stimulations every days. Results: Application of LFS significantly retarded the kindling acquisition and increased the number of stimulations to achieve different seizure stages [F(4,60)=10.9, P<0.0001]. LFS also prevented increment of slope of field excitatory postsynaptic potentials and population spike amplitude during kindling (P<0.001) (There was %88.6±1.7 increment in fEPSP and %94±2.3 increment in PS in kindled group and %3.5±.05 increment in fEPSP and %12.3±0.1 decrease in PS in kindled+LFS group). In addition, LFS prevented the marked increase in early (10-50 ms intervals) and late (300-1000 ms intervals) paired pulse depression induced by kindling significantly (P<0.01). Conclusion: According to obtained results, it may be suggested that LFS of perforant path has a significant antiepileptogenic effect on perforant path kindled seizures through inhibition of synaptic transmission in dentate gyrus. Meanwhile, LFS prevents compensatory increase in the paired pulse depression during kindling acquisition.
Tahereh Zeinali, Javad Mirnajafi-Zadeh, Vahid Sheibani, Mohammad Eza Palizvan, Mehdi Abbasnejad,
Volume 11, Issue 3 (12-2007)

Epilepsy is among the most common disorders of the central nervous system and there is not an absolute method for its treatment. It has been shown that each seizure has a depressing effect on the following seizure. Thus, finding the mechanisms responsible in this phenomenon can improve our knowledge toward new ways for epilepsy treatment. In this study, the role of adenosine A1 receptors in post seizure depressing period was investigated in amygdala kindling model of epilepsy. Methods: Rats were kindled by daily electrical stimulation of amygdala. At first, different groups of kindled animals were stimulated at different times after the first stimulation and the percent of suppression of seizure parameters were calculated. Then, 8-cyclopenthyl-1, 3-dimethylxanthine (CPT), a selective adenosine A1 receptor antagonist (50 and 200 μM) were intracerebroventricularly microinjected before the second stimulation and its effect on percent of suppression induced by the first stimulation was investigated. Results: In the second stimulation, applied at 10 and 30 min after the first stimulation, the seizure parameters were significantly reduced. CPT microinjection (50 and 200 μM) significantly decreased the percent of suppression of seizure parameters. This decrease was significant at 10 and 30 min after the first stimulation with compare to the groups received the drug solvent. Conclusion: Obtained results showed that endogenous adenosine has a role in post seizure depression period through A1 receptors. As the blocking of A1 receptors by CPT could not completely prevent this period, other factors may also play role in this suppression.
Fariba Zafari, Masome Sabetkasaei, Yousef Sadeghi, Mohammad Mohammad-Zade, Fateme Deljo,
Volume 11, Issue 4 (1-2008)

Introduction: The claustrum interconnects with the allocortical and neocortical regions and also projects to the hippocampus and the amygdala. .The role of claustrum in the complex partial seizure is not clear. Thus in this study the effect of amygdala lesion on anterior claustrum kindled seizures in rat were investigated. Methods: Male Wistar rats, weighting 250-300 g, were received DC current via a bipolar electrode which is inserted in right basolateral amygdala. A tripolar electrode for stimulation and electroencephalography recording in the right anterior claustrum has been fixed. After a 10 days period of surgical recovery, animals were received kindling stimulation (60Hz, 2s, 1 ms pulse duration) daily, and kindling parameters were measured. In the control group animals did not receive DC current. In the lesion groups (2 groups) animals received DC current both before kindling stimulation and after full kindled statement respectively. Results: Our result showed that amygdala lesion, were capable of delaying claustrum kindling. The delay in kindling was due to an increase in the stimulation trials required to kindle to seizure stages. Furthermore the effect of this lesion on established kindled seizures reduced the severity of claustrum by decrease the stage 5 duration and after discharge duration. Conclusion: amygdale lesion had no effect on the expression of generalized seizures and claustrum play an important role in the propagation of epileptic seizure. Whereas the amygdala has a facilitators role in propagation claustrum kindled seizure.
Somayeh Mongabadi, S.m.p. Firouzabadi, Javad Mirnajafi-Zadeh,
Volume 12, Issue 1 (5-2008)

IIntroduction: Repetitive transcranial magnetic stimulation (rTMS) modulates the excitability of cortical neural networks. The effect of rTMS on excitability of cortical networks depends on its frequency. According to the previous reports, a distinction is made between low (<1Hz) and high frequencies of rTMS. Low frequencies of rTMS inhibit seizure but high frequencies increase it. In the current study we tried to investigate the effect of different frequencies of rTMS on chemical kindling induced seizure in rats. Methods: Chemical kindling was induced by i.p. injections of penthylentetrazol (PTZ) 45 mg/kg, 3 times per week.Effect of different frequencies of rTMS (0.25, 1 and 5 Hz) on kindling acquisition was investigated. rTMS was applied 30 minutes after PTZ injections. Stimulation was delivered at motor threshold intensity (4s, 4 stimulus interval of 10 s). Results: Maximum stage of behavioral seizure decreased by 0.25 Hz rTMS and increased by 5 Hz rTMS. Stages 4 and 5 latencies were increased by 0.25 Hz rTMS and decreased by 5 Hz rTMS. Stage 5 duration was decreased by0.25Hz rTMS and increased by 5 Hz rTMS. Discussion: Our results showed that application of rTMS had significant effect on seizure parameters in acquisition period. Lower frequencies of rTMS seem to be more effective.
Azam Shafaie, Masoud Fereidoni, Ali Moghimi, Morteza Behnamrasooli,
Volume 12, Issue 4 (1-2009)

Introduction: In the Kindling-induced seizure model, low and repeated electrical or chemical stimulations, can elevate the neural network excitability and induce epileptiform seizures. Opioid receptors are widely distributed in different areas of the brain. On the other hand, morphine has paradoxical effects and induces elevation or alleviation of the pain sensation and excitability, at different doses. The present study is designed to investigate the effect of ultra low dose morphine on seizures induced by pentylentetrazol (PTZ). Methods: PTZ (32 mg/kg i.p.) was administered for 12 constitutive days to kindle the male Wistar rats (200-250 g). Animals were treated by saline or morphine (0.1 μg/kg, 1 μ g/kg, 10 μ g/kg and 10 mg/kg), 30 min before PTZ administration (n = 7-9) and seizure severity was recorded during 30 min after PTZ administrations. Results: Morphine at the dose of 10 mg/kg was able to elevate the seizure intensity and accelerate the kindling process (p<0.001), but at the dose of 10 μg/kg, attenuated the seizure intensity and kindling development (p<0.05). Conclusion: The reason for this paradoxical effect of morphine on PTZ-induced seizure could be that morphine, at ultra low doses, can elicit the stimulatory signaling pathway of Gs protein, rather than the inhibitory Gi pathway. It seems that ultra low does of morphine by inducing the activity of Gs signaling can lead to the attenuation of PTZinduced seizures, while activation of Gi signaling using ordinary doses of morphine can cause potentiation of PTZinduced seizures.
Maryam Zeraati, Javad Mirnajafi-Zadeh, Mohammad Javan, Saeed Semnanian, Simin Namvar,
Volume 14, Issue 2 (7-2010)

Introduction: Considering high prevalence of epileptic disease and considering that 40 percent of epileptic patients are resistant to drug therapy, it needs more researches to find new therapeutic ways. LFS is among the new methods for epilepsy treatments. One possible mechanism involved in the anticonvulsant effect of LFS is increased adenosine. Therefore, in this study the role of adenosine production from ATP by ectonucleotidase enzyme pathway in exerting the anticonvulsant effects of LFS were evaluated. Methods: Animals were kindled by electrical stimulation of perforant path in a rapid kindling manner (12 stimulation per day). One group of animals received LFS after kindling stimulation. In one another group, AOPCP a blocker of ectonucleotidase inhibitor was micro injected (50 micro molar) intra cerebro ventricular each day before LFS stimulation. Some group of animals were also received AOPCP (50 and 100 micro molar) but were not applied to LFS. Seizure behavior and electrophysiological parameters (including ADD and field potential) were recorded. Results: Like previous investigations, application of LFS, decreased all seizure parameters significantly. Microinjection of AOPCP had no significant effect on anticonvulsant actions of LFS. However microinjection of AOPCP at doses of 100 micro molar in animals that received just kindling stimulations, increased the seizure parameters significantly. Conclusion: The results show that adenosine production via ectonucleotidase enzyme pathway may has no role in anticonvulsant effects of LFS however endogenous adenosine produced through this pathway has an important role in kindling development.
Simin Namvar, Javad Mirnajafi-Zadeh, Mohammad Javan, Maryam Zeraati,
Volume 14, Issue 3 (10-2010)

Introduction: Application of low-frequency stimulation (LFS) is a new method for treatment of drug resistant epileptic patients. Previous studies demonstrated that activation of receptors coupled to Gi proteins is one of the mechanisms of the anticonvulsant effect of LFS. Thus, in this study, alterations in the expression of RGS4 and RGS10 proteins, as negative regulators of Gi proteins, were investigated. Methods: Animals were kindled by perforant path stimulation in a rapid kindling manner (12 stimulation per day, 1 ms pulse duration at 50 Hz). LFS (8 stimulation per day, 0.1 ms pulse duration at 1 Hz, 200 pulses) was applied to the perforant path 5 minute after the termination of kindling stimulations. After electrophysiological recordings for 6 days, the dentate gyrus of the animals was removed and RGS4 and RGS10 protein expression was studied by western blotting technique. Results: Application of LFS significantly retarded kindling acquisition and increased the number of stimulations to achieve different stages of seizure. LFS also significantly reduced after discharge duration. In addition, application of LFS after kindling stimulation reduced the expression of RGS4 and RGS10 proteins. Conclusion: Results of the present study showed that LFS has anticonvulsant effects on the perforant path kindling. Application of LFS following kindling stimulation reduced the expression of RGS4 and RGS10 proteins. Reduction of the expression of these proteins results in the longer activation of signaling pathways of Gi proteins, which may be responsible for LFS anticonvulsant effects.
Zohre Ghotbeddin, Javad Mirnajafi-Zadeh, Saeed Semnanian, Mahyar Janahmadi,
Volume 16, Issue 1 (4-2012)

Introduction: Many studies have shown that amygdala kindling produces synaptic potentiation by induction of changes in the neuronal electrophysiological properties and inward currents both in epileptic focus and in the areas which are in connection with the epileptic focus and have important role in seizure development and progression such as hippocampal CA1 region. However, cellular mechanisms of these processes are not clear. In the present study, changes in the electrophysiological properties of hippocampal CA1 pyramidal neurons following amygdala kindling were examined in rat. Methods: Animals were rapidly kindled by stimulation of right amygdala (12 stimulation per day, 1 ms pulse duration at 50Hz). Twenty-four hours after amygdala kindling, electrophysiological properties and inward currents of CA1 pyramidal neurons were assessed by using whole-cell patch clamp technique. Results: Amygdala kindling findings show that percentage broadening of the last spike compared to the first spike during a trains of action potentials was significantly increased in kindled rats (p<0.05). The number of rebound action potential was significantly increased from 1±1 in control rats to 6±1 in kindled rats (p<0.01). The amplitude of post stimulus afterhyperpolarization potential (Post AHP) following a trains of action potential was also significantly (p<0.05) increased in kindled group (-5±2mV) compared to normal rats (-3±1mV). Under voltage clamp condition, amygdala kindling produced a significantly larger inward current (-5344.25±33.19 pA, p<0.001) in CA1 pyramidal neurons compared to normal cells (-9203.6±44.99pA). Conclusion: The present findings show that amygdala kindling resulted in neuronal hyperexcitability through alteration of the electrophysiological characteristics possibly by increasing the inward currents in hippocampal CA1 pyramidal neurons.
Seyed Mehdi Beheshti Nasr, Ali Moghimi, Mohammad Mohammad-Zadeh,
Volume 16, Issue 3 (10-2012)

Introduction: Minocycline is a derivative of tetracycline that has anti-inflammatory, antiappoptic, antioxidant and neuroprotective effects. Since there is a relationship between cell death and seizure, the aim of this study was to examine the role of minocycline in development of amygdala kindling in Wistar rats. Methods: In this study, 21 rats were divided into three groups. After sterotaxic surgery and 1 week recovery period, rats received kindling stimulations (twice daily at 6 hour intervals). Group 1 (n=7) received daily kindling stimulations. Groups 2 (n=7) and 3(n=7) received saline (1 ml/kg) and minocycline (25 mg/kg), respectively, 60 min before kindling stimulation. Cumulative After discharge Duration (ADD), Cumulative Seizure duration (SD) and Seizure Stage (SS) were recorded and compared to the control group. Results: In group 3, intraperitoneal administration of minocycline for 10 days significantly reduced cumulative ADD (control group: 907.2±64.5, minocycline group: 717.8±67.9) [F(18, 216)=3.5, p<0.001] ،and cumulative SD (control group: 999.4±79.8, minocycline group: 776.1±77) [F(19, 228)=3.8, p<0.001] compared to control group (group 2). It also significantly increased the mean number of stimulations to achieve the seizure stage 3 (control group: 7.2±0.6, minocycline group: 11±1) (P<0.05), and 5 (control group: 10.7±0.1, minocycline group: 18.7±0.3) (P<0.001). Conclusion: According to the obtained results, application of minocycline increases the time required for amygdala kindling and may have anticonvulsant effects.
Amir Shojaei, Saeed Semnanian, Mahyar Janahmadi, Homeira Moradi, Seyad Mohammad Firoozabadi, Javad Mirnajafi-Zadeh,
Volume 19, Issue 1 (3-2015)

Introduction: 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. Materials and Methods: 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. Results: 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. Conclusion: 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.
Batool Kamali Manesh, Ehsan Mohebi, Hassan Azhdari Zarmehri, Ali Shamsizadeh, Mohammad Mohammad-Zadeh,
Volume 22, Issue 2 (6-2018)

Introduction: Epilepsy is one of the most common and chronic neurological disorders. It appears periodically and usually is concomitant with unpredictable seizures due to abnormal discharge of brain neurons. In this study, we investigated the anticonvulsant effect of ascorbic acid (AA) on seizures induced by pentylenetetrazole (PTZ) in male rats. Methods: In this study PTZ (37 mg/kg) was injected every other day to induce kindling in male rats. AA (12.5, 25 and 50 mg/kg) was administered into the right lateral ventricle 30 minute before every PTZ injection. The seizure parameters were measured during 30 min after PTZ injection. Results: Administration of 12.5 mg/kg of AA increased stage 4 latency compared to vehicle group. Conversely, 50 mg/kg of AA decreased stage 1 and 2 latency, increased stage 5 duration and decreased number of PTZ injections needed to achieve stage 5 seizure compared to vehicle treated animals. Conclusion: It seems that the AA has dual effects on seizure parameters induced by PTZ. Low doses (12.5 mg/kg) have protective effects while high doses (50 mg/kg) have proconvulsant effects on seizure.

Reza Naeimi, Maryam Ghasemi-Kasman, Sohrab Kazemi, Manouchehr Ashrafpour, Ali Akbar Moghadamnia, Fereshteh Pourabdolhossein,
Volume 22, Issue 2 (6-2018)

Introduction: Recently, herbal medicine is widely used as an alternative and complementary therapy in several neurological disorders such as epilepsy. The anti-inflammatory and neuroprotective effects of Zingiber officinale or ginger have been well-documented. The present study was designed to evaluate the effects of ginger extract pre-treatment on seizures behavior, neuronal density and astrocytes activation in pentylenetetrazol (PTZ)- induced kindling model. Methods: Kindling model was induced in mice by repetitive administration of PTZ at sub convulsive dose. Hydroalcoholic extract of ginger at doses of 25, 50 or 100 mg/kg were daily injected 10 days before PTZ injections and intraperitoneal administration of extract was continued 1h before each PTZ injection. Immunostaining against NeuN and GFAP as neuronal and astrocyte markers, respectively, was carried out on brain tissue sections. Results: Our data showed that ginger extract pre-treatment, especially at dose of 100 mg/kg, reduced the seizures behavior in PTZ receiving animals. Immunostaining against NeuN biomarker demonstrated that neuronal death was alleviated in animals under treatment of ginger extract. Furthermore, application of ginger extract attenuated the number of GFAP expressing cells in hippocampus of fully-kindled animals. Conclusion: Overall, our data suggest that ginger pre-treatment exerts significant neuroprotective effect by attenuation of astrocytes activation in PTZ-induced kindling model. It can be concluded that ginger might be used as effective supplementary agent in epileptic patients.

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