Pentylenetetrazole Injection Research Articles

Neuroprotective Effects of Low Dose Anandamide in Pentylenetetrazole-Induced Kindling in Rats

Anandamide (N-arachidonoylethanolamine) is an endogenous cannabinoid receptor CB1 ligand that exhibits neuroprotective effects in the brain. In this study, the effect of exogenously given anandamide on pentylenetetrazole (PTZ)-induced chemical kindling oxidative stress and brain damage in rats was studied. Rats were intraperitoneally (i.p.) injected with 35 mg/kg PTZ once every 48 hours for 12 times to induce seizures. Anandamide was i.p. given. 30 min prior to PTZ injection at 100 or 200 mg/kg. Injections of PTZ induced significant increase in brain lipid peroxidation (malondialdehyde: MDA), and nitric oxide associated with marked decrease in brain reduced glutathione (GSH). There were also significant decrements in acetylcholinesterase (AChE) concentration, butyrylcholinesterase (BChE) and paraoxonase-1 (PON-1) activities in brain tissue of PTZ injected rats. Meanwhile, there was no significant effect for PTZ on the concentration of brain neutrophil elastase. Anandamide administered at 100 and 200 mg/kg significantly decreased MDA and increased GSH contents and at 200 mg/kg significantly decreased nitric oxide in brain of PTZ-treated rats. The drug also caused significant increments in AChE concentration and PON-1 activity but had no significant effect on BChE or neutrophil elastase in rats treated with PTZ. Anandamide given at the dose of 200mg/kg significantly decreased the mean seizure scores over the study period by 22.3% and the frequency of myoclonic jerks and rearing (stage 3) by 56.7% compared with the vehicle-treated group. Anandamide given at 100 and 200 mg/kg completely inhibited the development of generalized tonic-clonic seizures (stage 5). It is concluded that in the PTZ-induced seizures, the cannabinoid receptor CB1 agonist anandamide decreases brain oxidative stress, neuronal injury, and exerts an antiepileptic activity.

Behavioral, electrophysiological and neuropathological characteristics of the occurrence of hypertension in pregnant rats

Pre-eclampsia (PE) affects approximately 2 to 8% of pregnant women, causing blood pressure above 140 × 90 mmHg and proteinuria, normally after the 20th gestation week. If unsuccessfully treated, PE can lead to self-limited seizures (Eclampsia) that could eventually result in death of the mother and her fetus. The present study reports an experimental model of preeclampsia hypertension in pregnant (HP) and non-pregnant (H) Wistar rats by partially clamping one of their renal arteries. Pregnant (P) and non-pregnant (C) controls were provided. Differently from controls (C and P), H and HP animals presented a steady rise in BP two weeks after renal artery clamping. Injection of pentylenetetrazol (PTZ) induced behavioral and electroencephalographic seizures in all groups, which were increased in number, duration, amplitude and power accompanied by decreased latency in HP animals (p < 0.05). Consistent results were obtained in in vitro experimentation. Immunohistochemistry of hippocampus tissue in HP animals showed decreased density of neurons nuclei in CA1, CA3 and Hilus and increased density of astrocytes in CA1, CA3 and gyrus (p < 0.05). The present findings show that the clamping of one renal arteries to 0.15 mm and PTZ administration were able to induce signs similar to human PE in pregnant Wistar rats.

Myricetin attenuates the severity of seizures and neuroapoptosis in pentylenetetrazole kindled mice by regulating the of BDNF-TrkB signaling pathway and modulating matrix metalloproteinase-9 and GABAA.

Currently available antiepileptic drugs are effective; however, frequently associated with adverse effects that limit their therapeutic value. Compounds that target the molecular events underlying epilepsy, with minor or no adverse effects, would be of clinical value. Matrix metalloproteinase-9 (MMP-9) and the brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) signaling pathway may be involved in epileptogenesis. The current study investigated the effects of the plant-derived hydroxyflavone, myricetin, in a pentylenetetrazole (PTZ)-induced mouse model of epilepsy. Mice received an intraperitoneal injection of 35 mg/kg body weight PTZ on alternate days (13 injections) and were observed for 30 min following each PTZ injection. Myricetin (100 or 200 mg/kg body weight) was administered orally to the treatment groups (n=18/group) for 26 days, 30 min prior to each PTZ injection. Treatment with myricetin reduced seizure and mortality rates. Increased apoptotic cell count and elevated expression levels of apoptotic proteins caused by PTZ kindling were downregulated following treatment with myricetin. The BDNF-TrkB signaling pathway and MMP-9 expression levels were regulated by myricetin. Expression of γ-aminobutyric acid A (GABA) receptor and glutamic acid decarboxylase 65, as well as the glutamate/GABA balance, were restored following treatment with myricetin. The results of the present study indicated that myricetin may exert protective effects by regulating the molecular events associated with epileptogenesis.

Effect of Artemisia persica on seizure severity and memory and learning disorders in pentylenetetrazole-kindled mice

The purpose of this study was to investigate the effect of hydroalcoholic extract of Artemisia persica (100, 200 and 400 mg/kg) on pentylenetetrazole-induced seizure and memory impairment. Sixty mice were assigned to seven groups. Pentylenetetrazole (35 mg/kg) was injected at 48 hours intervals for 9 days, and at 60 mg/kg on day 10 to induce seizure model. Different doses of A. persica extract were injected daily 30 min before pentylenetetrazole injection. Exposure of mice to extract significantly reduced the frequency of repeated spinning and jumping and tonic seizures in seizure model. In addition, the extract significantly reduced the increased levels of malondialdehyde in serum and brain. The extract significantly increased the serum and brain anti-oxidant capacity but had no significant effect on nitric oxide. The extract (100 mg/kg) significantly improved pentylenetetrazole-induced memory impairment. The hydro-alcoholic extract of A. persica has a protective effect against pentylenetrazole-induced seizure.&#x0D; Video Clip of Methodology:&#x0D; 1 min 56 sec: Full Screen Alternate

Effect of gabapentin on sleep patterns disturbed by epilepsy

For a long time, numerous sleep alterations induced by nocturnal epilepsy have been described. Such alterations include sleep fragmentation, decrement of sleep efficiency, increment of the wake time after sleep onset (WASO), increment of light sleep, and decrement of sleep depth. On the other hand, gabapentin (GBP), an antiepileptic drug analog of γ-aminobutyric acid (GABA) used as adjunctive and eventually, as a monotherapeutic treatment, induces a significant improvement in patients with both focal and secondarily generalized partial seizures. In experimental epilepsy models, this drug protects against pentylenetetrazol (PTZ)-induced convulsions. In consideration of such GBP properties, the aim of this work was to investigate its efficacy to protect against sleep disturbances provoked by convulsive seizures induced by the administration of PTZ.Nine-hour (9-hour) polygraphic studies were carried out in chronically implanted male adult Wistar rats separated into 4 different groups of 6 individuals. Control recordings in each group were done after saline administration. One group received a SC Subcutaneous (SC) injection of 50 mg/kg of PTZ alone while the other three groups were injected with either 15, 30, or 60 mg/kg IP Intraperitoneal (IP) of GBP 30 min prior to PTZ (50 mg/kg SC) administration.Animals displayed the whole range of electrophysiological and behavioral manifestations of the disease during the epileptic episodes induced by PTZ administration, and the states of vigilance were significantly altered. Insomnia occurred immediately after PTZ injection preceding the appearance of the first epileptic symptoms. Thus, both slow wave sleep (SWS) and rapid eye movement sleep (REM sleep) were completely inhibited during a relatively long period of time.The disturbing effects of epilepsy on sleep decreased when animals were under GBP treatment. Improvement of sleep was dependent on the administered dose of this antiepileptic drug.

Investigating the effect of rTMS on acute pentylenetetrazol injection induced seizures in rat

Absence epilepsy is a kind of epileptic syndrom which has not an absolute treatment. So much research to find new ways to treat the disease is in progress. On the other hand, it has been shown that application of repetitive transcranial magnetic stimulation (rTMS) can be applied through magnetic induction causes changes in neuronal excitability. In the present study we investigated the effect of particular pattern of rTMS on absent epileptic model .The epileptic model was induced by an acute injection of pentylenetetrazol in rats. The inhibitory effects of rTMS were investigated by evaluating 4 convulsive index including the latency until onset of stage 2 and 4, duration of generalized seizures and maximum seizure stage. Result indicated that application of particular pattern of rTMS 3 minute before injection of PTZ significantly inhibited PTZ-induced convulsions.

Discrepancies of Notch 1 receptor during development of chronic seizures.

The critical role of Notch signaling has been shown in the pathogenesis of some neurological disorders including schizophrenia, epilepsy and Alzheimer's disease. This study was aimed to evaluate the role of Notch 1 receptor in epileptogenesis as well as seizure characteristics. The animals were divided into three groups of sham, early stage and end stage. In sham group: Normal saline was injected intraperitoneally (ip) in the same as protocol of pentylenetetrazol (PTZ) injection. PTZ was injected (ip) every 48 hr over a period of 1 week in the group of early stage and over a period of 4 weeks in the end stage. The gene expression as well as distribution of Notch 1 receptor was assessed in the parietal cortex and hippocampus. In addition, the effect of agonist or antagonist of Notch 1 receptor was assessed on the epileptic discharges induced by PTZ injection. The gene expression of Notch 1 decreased in the hippocampus significantly in the end-stage group compared with sham, and early groups. Furthermore, distribution of Notch 1 receptor increased in the somatosensory cortex and decreased in the CA1 hippocampal area in the end-stage group. Intraventricular microinjection of Notch 1 agonist significantly increased the amplitude as well as frequency of spikes and decreased the latency of first epileptic discharges. Our findings illustrate the critical role of Notch signalling as a potential pathway in the epileptogenesis during development of chronic seizures.

A novel oxazolidinone derivative PH192 demonstrates anticonvulsant activity in vivo in rats and mice

The pharmacotherapeutic management of seizure disorders with currently available medications is not optimal due to side effects and failure of some patients to respond to all available medications. As such there is the need to develop new antiseizure drugs by looking at new chemical classes of compounds. We recently screened, in vitro, a new class of compounds, the oxazolidinones, for actions in the brain that may indicate potential for antiseizure activity. A few compounds were identified with such a potential. Here we tested whether one of these lead compounds, PH192, will exhibit in vivo antiseizure activity using chemically- and electrically- induced seizures models in mice and rats. Out of 5 compounds tested, all of them had minimal neurotoxicological effects in mice, with PH192 being the best, with comparable efficacy (ED50) and toxicity (TD50) to only levetiracetam. Intraperitoneal (IP) pretreatment with PH192 produced a dose-dependent protection of mice from seizures induced using the 6 Hz stimulation protocol with an estimated ED50 of 34.5 mg/kg in mice and about 90 mg/kg in rats and a neurotoxic dose >500 mg/kg in mice, yielding a calculated neuro (protective) index of >14.7. When pretreated with 100 mg/kg PH192 for 30 min, about 75% of mice were protected from 6 Hz-induced seizures. When rats were pretreated for 30 min with PH192, 66.6% of rats were protected from seizures induced using the 6 Hz stimulation protocol while 83.3% were protected using the maximal electroshock (MES) stimulation protocol. Pentylenetetrazole (PTZ) injection at 50, and 100 mg/kg produced stage 5 seizures in all rats. Thirty minutes IP pretreatment of rats with 100 mg/kg PH192 protected 80% of rats from the PTZ-induced seizures, a level of protection similar to that obtained with a reference antiepileptic drug (AED) phenytoin (40 mg/kg), that is used clinically for the treatment of various seizure disorders. The results of these studies indicate that PH192 protects against both chemically- and electrically-induced seizures with little central nervous system side effects. This suggests that the oxazolidinone pharmacophore has potential for discovering new antiepileptic drugs with possibly minimal central side effects.

Transient Switching of NMDA-Dependent Long-Term Synaptic Potentiation in CA3-CA1 Hippocampal Synapses to mGluR1-Dependent Potentiation After Pentylenetetrazole-Induced Acute Seizures in Young Rats.

The mechanisms of impairment in long-term potentiation after status epilepticus (SE) remain unclear. We investigated the properties of LTP induced by theta-burst stimulation in hippocampal slices of rats 3h and 1, 3, and 7 days after SE. Seizures were induced in 3-week old rats by a single injection of pentylenetetrazole (PTZ). Only animals with generalized seizures lasting more than 30min were included in the experiments. The results revealed that LTP was strongly attenuated in the CA1 hippocampal area after PTZ-induced SE as compared with that in control animals. Saturation of synaptic responses following epileptic activity does not explain weakening of LTP because neither the quantal size of the excitatory responses nor the slopes of the input-output curves for field excitatory postsynaptic potentials changed in the post-SE rats. After PTZ-induced SE, NMDA-dependent LTP was suppressed, and LTP transiently switched to the mGluR1-dependent form. This finding does not appear to have been reported previously in the literature. An antagonist of NMDA receptors, D-2-amino-5-phosphonovalerate, did not block LTP induction in 3-h and 1-day post-SE slices. An antagonist of mGluR1, FTIDS, completely prevented LTP in 1-day post-SE slices; whereas it did not affect LTP induction in control and post-SE slices at the other studied times. mGluR1-dependent LTP was postsynaptically expressed and did not require NMDA receptor activation. Recovery of NMDA-dependent LTP occurred 7day after SE. Transient switching between NMDA-dependent LTP and mGluR1-dependent LTP could play a role in the pathogenesis of acquired epilepsy.

The Effects of the Peroxisome-Proliferator Activated Receptor-alpha Agonist, Fenofibrate, on the Antioxidant Capacity of the Brain in Pentylenetetrazol Kindling Seizures in Mice

It has been demonstrated that peroxisome-proliferator activated receptor-alpha (PPARα) has a potent neuroprotective role in various pathological events of the nervous tissue. Since oxidative damage is associated with development of seizure, we aimed to examine whether the PPARα agonist, fenofibrate, exerts protective effects against the repeated seizures in pentylenetetrazol (PTZ) kindling model in mice through improving the brain antioxidant capacity. The experiment was carried out in two groups of mice (each group, n = 12): PTZ-kindled mice and fenofibrate-treated kindled mice. Repetitive intraperitoneal injections of PTZ (65 mg/kg) once every 48 h were used to achieve the kindling seizures till day 21. The mice were administered orally fenofibrate (30 mg/kg/day) during the test. Latency and the brain activities of catalase and superoxide dismutase (SOD) as well as the brain content of reduced glutathione (GSH) were determined at termination of the experiment. The latency following the last injection of PTZ was considerably decreased in untreated kindled mice (49 ± 8 s), whereas fenofibrate treatment prevented this reduction in kindled mice (105 ± 16 s). Treatment with fenofibrate significantly increased the GSH content in kindled mice (20.22 ± 9.87 nmol/mg protein) compared to untreated kindled mice (5.37 ± 0.84 nmol/mg protein), (p < 0.05). Likewise, treatment with fenofibrate considerably increased the activities of catalase and SOD in kindled mice compared to untreated kindled mice by 78% and 55%, respectively. In view of the critical protective role of antioxidants in seizures, the findings of the present study suggested that the PPARα agonist, fenofibrate, might modulate the seizure behaviors in the PTZ kindling model in mice through improving the brain antioxidant capacity.

Peroxisomal Proliferator-Activated γ-Receptors: Participation in the Anti-Seizure Effects of Transcranial DC Stimulation of the Cerebellum

In rats with the kindling syndrome induced by i.p. injections of pentylenetetrazol (PTZ; 30.0 mg/kg daily, for three weeks), the latent period of seizures induced by a test injection of PTZ (30 mg/kg) increased significantly (by 22.5% on average P < 0.05 vs. control) after transcranial DC stimulation (TDCS, 600 μA, 10.0 min, cathode on the skull surface) oriented to the cerebellar cortex. Such stimulation prevented the development of generalized clonico-tonic seizures and decreased the duration of ictal discharges about two times (P < 0.05). After administration of an antagonist of peroxisomal proliferator-activated γ-receptors (PPARγ), bisphenol A diglycidyl ether (2,2’-[(1-methylethylidene) bis(4,1-phenyleneoxymethylene)] bis-oxirane, BADGE, 100 mg/kg, i.p.), TDCS did not lead to an increase in the latency of test PTZ-induced seizures. The latter parameter was shorter than that in the TDCS group with no injection of the γ receptor antagonist and did not differ from the control. The seizure latency in this case was smaller than that in the TDCS group (by 31.6% on average, P < 0.05), and the seizure severity was greater by 52.3% (P < 0.05).

The Protective Effect of Auraptene Against Oxidative Stress and Pentylenetetrazol-Induced Chemical Kindling in Mice.

It is believed that some pitfalls in the treatment of epilepsy such as serious side effects of medications and drug resistance may be resolved by natural compounds. Auraptene belongs to coumarins and is found in citrus peel. We hypothesized that auraptene might have anticonvulsant properties. Kindling was induced by repeated intraperitoneal (IP) injections of pentylenetetrazol (PTZ, 35 mg/kg) with two-day intervals for 24 days in male albino mice. Three groups received IP injections of auraptene (12.5, 25, and 50 mg/kg). Three control groups received vehicle, diazepam (3 mg/kg, IP), and vitamin E (150 mg/kg, IP). Seizure-related behaviors were recorded for 30 min after PTZ injection. Moreover, malondialdehyde and reduced glutathione (GSH) were measured in the brain. The results indicated that auraptene at the dose of 12.5 mg/kg and vitamin E significantly prolonged the latency to stage 2 of seizures (P < 0.01). Auraptene at the doses of 25 mg/kg and 50 mg/kg, prolonged the latency to stage 4 (P < 0.01) and reduced stage 5 duration of seizures (P < 0.01). All doses of auraptene reduced median of seizure scores (P < 0.01). The kindled control group had MDA levels similar to intact animals but had a lower concentration of GSH (P < 0.001). None of the tested compounds changed the malondialdehyde concentration significantly. However, auraptene at the dose of 50 mg/kg and vitamin E increased GSH levels (P < 0.05). The results suggest that auraptene had anticonvulsant effects in PTZ-induced chemical kindling that was mediated by mechanisms other than the antioxidant effect of auraptene.

Myristica Fragrans Houtt Extract Attenuates Neuronal Loss and Glial Activation in Pentylenetetrazol-Induced Kindling Model.

Inflammatory reactions are closely associated with the development and progression of epilepsy. It has been shown that inhibition of pro-inflammatory cytokines, which are released from activated astrocytes and microglia, are considered to be an effective therapeutic approach for the treatment of epileptic disorders. Regarding the anti-inflammatory effects of nutmeg (Myristica fragrans Houtt), the present study was designed to investigate whether the nutmeg ethanolic extract could exert anticonvulsant and inhibitory effects on glial activation in pentylenetetrazol (PTZ)-induced mice model of kindling. Ethanolic extract of nutmeg was administrated intraperitoneally (i.p.) 1 hour before PTZ injection or one week before PTZ as a separate group, to become fully-kindled. The chemical components of nutmeg extract were analyzed by gas chromatography mass spectrometry (GC-MS). Immunostaining against neuronal and glial markers was performed on hippocampus sections. GC-MS data indicated that the main components of nutmeg extract are myristic acid (39.93%), elemicin (22.16%) and myristicin (11.17%). Behavioral studies showed that pre-treatment of nutmeg extract effectively reduced seizures behavior, decreased cell death, and ameliorated glial activation that is followed by PTZ administration. In conclusion, nutmeg extract might be regarded as a useful supplementary agent in epilepsy treatment through its attenuation of neuronal loss and glial activation.

Effects of low-frequency repetitive transcranial magnetic stimulation on depression- and anxiety-like behaviors in epileptic rats.

Low-frequency repetitive transcranial magnetic stimulation (rTMS) has been considered as a treatment option for depression and anxiety. However, its role in epilepsy comorbid with depression and anxiety is unclear. Therefore, we evaluated whether low-frequency rTMS can alleviate depression- and anxiety-like behavior in epileptic rats. Forty-eight adult rats were allocated at random to four groups: Control, Pentylenetetrazol (PTZ), PTZ-rTMS and PTZ-Sham. The control group received intraperitoneal injections of normal saline, while the other groups received intraperitoneal injections of pentylenetetrazol (35 mg/kg/d) once a day for 15 days. Low-frequency rTMS or sham stimulation were administered to the PTZ-rTMS and PTZ-Sham group, respectively, over the two-week period. The open-field test (OFT), elevated plus-maze test (EPM) and forced swimming test (FST) were carried out before the experiment, on the 8th and 15th day to assess depression- and anxiety-like behavior in the rats. Two weeks of low-frequency rTMS treatment could not impair the increases of seizure severity in epileptic rats. However, relative to the PTZ and PTZ-Sham group, the two-week low-frequency rTMS treatment significantly reduced the immobility time in the forced swimming test and attenuated the progressive decrease in total distance traveled, frequency of rearing, velocity in the open-field test, number of entries in the open arms (%) and the time spent in the open arms (%) in the elevated plus-maze test of the PTZ-rTMS group. We proposed that low-frequency rTMS can benefit epileptic rats via amelioration of comorbid depression and anxiety, but it can not alleviate the seizure severity.

Effects of Leontice leontopetalum and Bongardia chrysogonum on oxidative stress and neuroprotection in PTZ kindling epilepsy in rats

We investigated the effects of Leontice leontopetalum and Bongardia chrysogonum on apoptosis, gamma-aminobutyric acid (GABAA) receptor positive cell number, cyclin-B1 and bcl-2 levels and oxidative stress in pentylenetetrazol (PTZ) kindling in rats. Kindling was produced by subconvulsant doses of PTZ treatments in rats. Wistar albino rats were divided into 4 groups; Control, PTZ treated (PTZ), PTZ+L. leontopetalum extract treated (PTZ+LLE) and PTZ+B. chrysogonum extract treated (PTZ+BCE) groups. Extracts were given a dose (200 mg/kg) 2h before each PTZ injection. PTZ treatment significantly decreased the glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) activities and bcl-2 levels and increased the total oxidant status (TOS), malondialdehyde (MDA), cyclin B1, oxidative stress index (OSI) and number of neurons that expressed GABAA receptors when compared to the control. LLE and BCE possessed antioxidant activity in the brain and ameliorated PTZ induced oxidative stress, decreased cyclin-B1, increased bcl-2 levels, and kept the GABAA receptor number similar to that of the control despite the PTZ application.

Effect of Nobiletin on Experimental Model of Epilepsy.

BackgroundThe effects of nobiletin, a plant-derived flavonoid was examined against pentylenetetrazole (PTZ)-induced seizures. The study also aimed to assess whether nobiletin potentiated the effects of antiepileptic drug clonazepam (CZP).MethodsPTZ (92 mg/kg, subcutaneous) was used to induce seizures in mice. Treatment groups (n = 18/group) received nobiletin (12.5, 25, or 50 mg/kg) via oral gavage for 6 consecutive days and 45 min prior to PTZ injection. CZP (0.015-2.0 mg/kg) was administered 15 min prior to PTZ. Skeletal muscle strength was assessed by measuring grip strength and Chimney test was performed to study the motor performance in animals. TUNEL assay was done to study neuro-apoptosis. RT-PCR and Western blot analysis were performed for assessment of mRNA and protein expressions.ResultsNobiletin and CZP improved muscle strength and motor coordination and reduced seizure severity significantly. The administration of nobiletin and CZP, individually or in combination, downregulated seizure-induced increases in apoptotic cell count and apoptotic protein expression, modulated the expression of gamma-aminobutyric acid (GABA)A and glutamate decarboxylase 65 and restored the glutamate/GABA balance. Nobiletin and CZP administration significantly upregulated phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling.ConclusionNobiletin exerted protective effect against seizures by regulating signaling pathways associated with epileptogenesis and potentiated the effects of CZP.

Changes in Functional Properties of Rat Hippocampal Neurons Following Pentylenetetrazole-induced Status Epilepticus

Pathophysiological remodeling processes following status epilepticus (SE) play a critical role in the pathophysiology of epilepsy but have not yet been not fully investigated. In the present study, we examined changes in intrinsic properties of pyramidal neurons, basal excitatory synaptic transmission, and short-term synaptic plasticity in hippocampal slices of rats after SE. Seizures were induced in 3-week-old rats by an intraperitoneal pentylenetetrazole (PTZ) injection. Only animals with generalized seizures lasting more than 30 min were included in the experiments. We found that CA1 pyramidal neurons became more excitable and started firing at a lower excitatory input due to a significant increase in input resistance. However, basal excitatory synaptic transmission was reduced in CA3-CA1 synapses, thus preventing the propagation of excitation through neural networks. A significant increase in paired-pulse facilitation 1 d after SE pointed to a decrease in the probability of glutamate release. Increased intrinsic excitability of neurons and decreased synaptic transmission differentially affected the excitability of a neural network. In terms of changes in seizure susceptibility after SE, we observed a significant increase in the maximal electroshock threshold 1 day after SE, suggesting a decrease in seizure susceptibility. However, after 1 week, there was no difference in seizure susceptibility between control and post-SE rats. The effects of SE on functional properties of hippocampal neurons were transient in the PTZ model, and most of them had recovered 1 week after SE. However, some minor alterations, such as smaller amplitude field potentials, were observed 1 month after SE.

Detection of Hyperexcitability by Functional Magnetic Resonance Imaging after Experimental Traumatic Brain Injury.

Diagnosis of ongoing epileptogenesis and associated hyperexcitability after brain injury is a major challenge. Given that increased neuronal activity in the brain triggers a blood oxygenation level-dependent (BOLD) response in functional magnetic resonance imaging (fMRI), we hypothesized that fMRI could be used to identify the brain area(s) with hyperexcitability during post-injury epileptogenesis. We applied fMRI to detect onset and spread of BOLD activation after pentylenetetrazol (PTZ)-induced seizures (PTZ, 30 mg/kg, intraperitoneally) in 16 adult male rats at 2 months after lateral fluid percussion (FPI)-induced traumatic brain injury (TBI). In sham-operated controls, onset of the PTZ-induced BOLD response was bilateral and first appeared in the cortex. After TBI, 5 of 9 (56%) rats exhibited ipsilateral perilesional cortical BOLD activation, followed by activation of the contralateral cortex. In 4 of 9 (44%) rats, onset of BOLD response was bilateral. Interestingly, latency from the PTZ injection to onset of the BOLD response increased in the following order: sham-operated controls (ipsilateral 132 ± 57 sec, contralateral 132 ± 57 sec; p > 0.05) < TBI with bilateral BOLD onset (ipsilateral 176 ± 54 sec, contralateral 178 ± 52 sec; p > 0.05) < TBI with ipsilateral BOLD onset (ipsilateral 406 ± 178 sec, contralateral 509 ± 140 sec; p < 0.05). Cortical lesion area did not differ between rats with ipsilateral versus bilateral BOLD onset (p > 0.05). In the group of rats with ipsilateral onset of PTZ-induced BOLD activation, none of the rats showed a robust bilateral thalamic BOLD response, only 1 of 5 rats had robust ipsilateral thalamic calcifications, and 4 of 5 rats had perilesional astrocytosis. These findings suggest the evolution of the epileptogenic zone in the perilesional cortex after TBI, which is sensitive to PTZ-induced hyperexcitability. Further studies are warranted to explore the evolution of thalamo-cortical pathology as a driver of epileptogenesis after lateral FPI.

140. A novel pre-eclampsia model induced by renal artery clipping

Background Pre-eclampsia affects approximately 2–8% of pregnant women, causing proteinuria and blood pressure above 140 × 90 mmHg after the 20th week of gestation. If left untreated, PE can lead to the occurrence of self-sustained seizures (Eclampsia) that could eventually evolve to coma, and death of the mother and fetus. In the present study, an experimental model of hypertension was induced in pregnant rats that, later, received a seizure-trigger injection of pentylenetetrazol (PTZ) aiming to mimetize the eclampsia clinical picture. Methods Wistar rats were divided into four groups: non-pregnant (NP), pregnant (P), hypertensive (H) and pregnant hypertensive (HP). Hypertension (H and HP) was induced via clipping of the left renal artery. Subsequently, all animals were injected with PTZ and behavioral and electroencephalographic (EEG) changes were recorded. Results In opposition to control animals (NP and P), those from the H and HP groups presented a steady increase in BP that was first noticed two weeks after the renal artery clipping. PTZ injection at pregnancy days 18, 19 and 20 was able to induce behavioral and electrographic seizures in all groups although the number and the duration of each fit were higher in HP animals when compared to other groups. Besides, EEG analysis revealed that signal power and amplitude during the seizure events were significantly higher in the HP group. Conclusion Renal artery clipping in pregnant female rats was able to induce signs similar to those observed in preeclampsia. Besides, PTZ administration was able to induce behavioral and electrographic seizures significantly more intense in the HP group than those observed in the control groups (NP, P, H).

Cannabis sativa Increases Seizure Severity and Brain Lipid Peroxidation in Pentylenetetrazole-Induced Kindling in Rats

The effect of Cannabis sativa extract on chemical kindling induced in rats by the repeated intraperitoneal (ip) injections of pentylenetetrazole (PTZ) was studied. Rats were treated with PTZ (35 mg/kg) once every 48 hours for 12 times alone or with ip Cannabis sativa (20 mg/kg expressed as Δ9-THC content) 30 min prior to PTZ injection. Seizures were recorded for 20 minutes. Control rats received ip saline. Cannabis treatment caused significant elevation of mean seizure score as compared to PTZ only group after the 5th, 6th and 7th PTZ repeated injections during seizure development. In particular, cannabis caused significant elevation in the frequency of myoclonic jerks, rearing (stage 3), turn over onto one side position and back position (stage 4), and generalized tonic-clonic seizures (stage 5) compared with the PTZ only group. PTZ caused significant elevations in brain lipid peroxidation (malondialdehyde), and nitric oxide along with deceased reduced glutathione level. In addition, brain acetylcholinesterase (AChE) activity significantly decreased compared to control value after PTZ treatment. Cannabis given to PTZ treated rats caused significant increase in brain malondialdehyde and AChE activity compared to PTZ only group. Reduced glutathione level was restored by cannabis. Histopathological studies indicated the presence of spongiform changes, degenerated and necrotic neurons, inflammatory cells, and gliosis in cerebral cortex and degeneration of some Purkinje cells in the cerebellum in both PTZ- and cannabis-PTZ-treated groups. It is concluded that in an epilepsy model induced by repeated PTZ administration, cannabis increased lipid peroxidation and mean seizure score.