Effect and Mechanism of Epigallocatechin-3-gallate on Learning and Memory Abilities of Epileptic Rats / 中国实验方剂学杂志

ObjectiveTo investigate the effects of epigallocatechin-3-gallate （EGCG） on learning and memory abilities of amygdala electrical kindling-induced epilepsy in rats and its mechanism. MethodMale SD rats were randomly divided into the normal group， model group， intervention group （model+25 mg·kg-1 EGCG）， and EGCG group （25 mg·kg-1 EGCG）. Rats in the EGCG group were only given EGCG intraperitoneal injection， those in the normal group were only given electrode implantation， and those in the other experimental groups were given amygdala electrical kindling stimulation to establish a chronic kindling epilepsy model. EGCG was injected intraperitoneally daily before electrical stimulation. Twenty-four hours after the last electrical stimulation， the escape latency and percentage of target quadrant were recorded by the Morris water maze. Twenty-four hours after the behavioral test， rats in each group were sacrificed by decapitation. The number of hippocampal neurons was observed by Nissl staining. The thickness of postsynaptic density in the hippocampus， synaptic cleft， length of active zone and the curvature of synaptic interface were observed by transmission electron microscopy （TEM）. The expressions of synapse-related proteins synaptotagmin （Syt）， postsynaptic density-95 （PSD-95） and Kalirin-7 in the hippocampus were examined by Western blot. ResultCompared with those in the normal group， the escape latency was significantly prolonged （P<0.05， P<0.01） and the target quadrant ratio was significantly decreased in the model group （P<0.05）. The number of hippocampus neurons decreased significantly （P<0.01）. The synaptic cleft of the hippocampus was widened significantly， and the length of active zone and the thickness of postsynaptic density were significantly decreased （P<0.05， P<0.01）. The expressions of synapse-related proteins Syt， PSD-95 and Kalirin-7 in the hippocampus were significantly decreased （P<0.05，P<0.01）. Compared with those in the model group， the escape latency was significantly shortened and the percentage of target quadrant was significantly increased in the intervention group （P<0.05， P<0，01）. The number of hippocampal neurons significantly increased （P<0.01）. The synaptic cleft of the hippocampus was significantly shortened， and the length of active zone and postsynaptic density were significantly increased （P<0.05， P<0.01）. The expressions of synaptic related proteins Syt， PSD-95 and Kalirin-7 were significantly increased （P<0.05， P<0.01）. ConclusionEGCG can effectively improve cognitive dysfunction after epilepsy. Its protective effect may be achieved by protecting the ultrastructure of hippocampal synapses and regulating the expressions of synapse-related proteins Syt， PSD-95 and Kalirin-7.

Manifestaciones neurológicas de la COVID-19 / Neurological manifestations of COVID-19

Objetivo: Describir la fisiopatología de las manifestaciones neurológicas por infección con COVID-19. Método: Revisión sistemática de 22 articulos relacionados con el objetivo de investigación, procedentes de la base de datos PubMed. Resultados: Dentro de las manifestaciones clínicas del COVID-19 en el SNP, se hallaron en los reportes clínicos, disminución parcial de la capacidad de percibir olores, denominada hiposmia y reducción total de la misma, denominada anosmia, así mismo otros pacientes o en los mismos que reportaron el anterior síntoma, refirieron haber perdido la capacidad para distinguir sabores, así la hipogeusia, y la ageusia también iban de la mano con la hiposmia. Conclusión: Se ha demostrado que el SARS-CoV-2 tiene un tropismo por las células del sistema nervioso, lo cual significaría una afectación al sistema nervioso que demás puede ser afectado por la tormenta de citoquinas, que a su vez pueden desarrollar un daño directo al parénquima neuronal.

Objective: To describe the pathophysiology of neurological manifestations due to infection with COVID-19. Methods: Systematic review of 22 articles related to the research objective, from the PubMed database. Results: Among the clinical manifestations of COVID-19 in the PNS, in the clinical reports, partial reduction of the ability to perceive odors, called hyposmia and total reduction of the same, called anosmia, as well as other patients or in the same patients who reported the previous symptom, reported having lost the ability to distinguish flavors, thus hypogeusia and ageusia also went hand in hand with hyposmia. Conclusion: SARS-CoV-2 has been shown to have a tropism for nervous system cells, which would mean an affectation to the nervous system that can be further affected by the cytokine storm, which in turn can develop direct damage to the neuronal parenchyma.

The antiepileptic activity of Safranal in kindling model of epilepsy in male rats

Abstract Recent studies suggested that safranal exerts anticonvulsant properties. The present study aimed to investigate the effect of safranal on epileptic activities in the amygdala electrical kindling model in male rats. Animals were implanted with a recording electrode on the skull and a tripolar in the amygdala. After 10 days of recovery, the afterdischarge (AD) threshold of each animal was determined and stimulated once daily the AD threshold for full kindling development. Then, parameters including afterdischarge duration (ADD), stage 4 latency (S4L), stage 5 duration (S5D), and stimulation threshold were determined before and after injection of safranal (0.05, 0.1, 0.2 ml/ kg; i.p). While the dose of 0.05 ml/kg had no significant effect, the dose of 0.1 ml/kg increased the AD threshold as well as S4L and decreased the S5D (P<0.05). Injection of 0.2 ml/kg of the safranal significantly decreased the ADD and S5D (P<0.05) and 83.3% of animals had no stage 4 and stage 5 of kindling (P<0.001). Based on the obtained data safranal has anticonvulsant effects dosedependently. It seems that a dose of 0.2 ml/kg is the minimum effective dose. Further investigation is warranted to conduct the clinical implications for the treatment of epileptic disorders

Modeling of post-traumatic epilepsy and experimental research aimed at its prevention

Research on the prevention of post-traumatic epilepsy (PTE) has seen remarkable advances regarding its physiopathology in recent years. From the search for biomarkers that might be used to indicate individual susceptibility to the development of new animal models and the investigation of new drugs, a great deal of knowledge has been amassed. Various groups have concentrated efforts in generating new animal models of traumatic brain injury (TBI) in an attempt to provide the means to further produce knowledge on the subject. Here we forward the hypothesis that restricting the search of biomarkers and of new drugs to prevent PTE by using only a limited set of TBI models might hamper the understanding of this relevant and yet not preventable medical condition.

How to prevent the malignant progression of bipolar disorder

There is increasing recognition that, in a high percentage of cases, bipolar disorder is a progressive illness. Multiple types of sensitization (or increased reactivity to repetition of the same stimulus) drive illness progression. One of the clearest is that of episode sensitization, where increased numbers of prior episodes are associated with: faster recurrences; more dysfunction; disability; social, educational, and employment deficits; suicide; medical comorbidities; cognitive dysfunction; and an increased incidence of dementia in old age. Repetition of stressors and bouts of substance abuse can also result in sensitization. Each type of sensitization appears to have an epigenetic basis, such that preventing sensitization should minimize the accumulation of adverse epigenetic chemical marks on DNA, histones, and microRNA. New data emphasize the importance of early, consistent intervention after an initial manic episode. The cognitive dysfunction associated with a first episode improves only if there are no further episode recurrences during the next year. A randomized study has also shown that comprehensive multimodal prophylactic intervention for 2 years leads to improvements in illness course extending over a total of 6 years. Intensive treatment of the earliest stages of bipolar disorder can thus exert lasting positive effects on the course of illness.

Modification of 6 Hz corneal kindled mouse model for drug-resistant epilepsy and its treatment by three traditional Chinese medicine prescriptions / 药学学报

Drug-resistance is a challenge in the treatment of epilepsy, and traditional Chinese medicine (TCM) prescription may have a potential in therapy of the epilepsy. Here we established a modified 6 Hz corneal kindled mouse model of epilepsy, and verified its drug-resistance to four commonly used western medicines. We evaluated the efficacy of three classical TCM prescriptions in this drug-resistant epilepsy model. The results showed that:① most C57BL/6J mice with stimulation current intensity at 44 mA (8 out of 10) were fully kindled, while none ICR mice with stimulation current intensity at 44 mA or C57BL/6J mice with stimulation current intensity at 24 mA were fully kindled. Fully kindled mice exhibited epileptic electroencephalograms after 44 mA and 6 Hz corneal kindling stimulation and increased activation of astrocytes in the hippocampus (by staining the glial fibrillary acidic protein); ② 50 mg·kg-1 phenytoin sodium, 100 mg·kg-1 valproic acid sodium and 15 mg·kg-1 lamotrigine had no significant effects on the drug-resistant seizures in 6 Hz corneal kindled C57BL/6J mice, while 100 mg·kg-1 levetiracetam significantly reduced the seizure stage (P P -1) and Tian-Ma Gou-Teng decoction (14.82 or 44.46 g·kg-1), had no significant effects on the drug-resistant seizures in 6 Hz corneal kindled C57BL/6J mice, while TCM prescription Feng-Yin decoction (19.11 g·kg-1) significantly reduced both the seizure stage (P P < 0.05) in it. Thus, the modified 6 Hz corneal kindled C57BL/6J mouse model is an excellent drug-resistant epilepsy model, Feng-Yin decoction have antiepileptic effects on it, suggesting Feng-Yin decoction may be an effective TCM prescription for clinical treatment of drug-resistant epilepsy.

Changes in expression of repressor element silencing transcription factor in rapid amygdala kindling epilepsy rats / 中国比较医学杂志

Objective To detect changes in expression of repressor element silencing transcription factor(REST) in rapid amygdala kindling epilepsy rats. Methods Adult Sprague-Dawley rats were randomly divided into a sham group (group S),epilepsy 2 h group(group EP-2 h),epilepsy 14 d group(group EP-14 d),and epilepsy 35 d group(group EP-35 d). An experimental epilepsy kindling model of the amygdala was established by electrical stimulation. After 2 h, 14 d,and 35 d,rats were perfused and their brains were fixed and frozen for coronal sections. Immunohistochemistry was used to detect expression of REST and the neuron specific nuclear protein, NeuN. Results Expression of REST was significantly increased in the CA1, CA3, and dentate gyrus regions in groups EP compared with group S(P < 0.05), particularly in group EP-2 h. In contrast,NeuN staining was significantly decreased in groups EP compared with group S. Visible neuronal loss was observed in the hippocampus of the EP-35 d group. Conclusions Up-regulation of REST in rat hippocampus may be involved in epileptogenesis.

Montelukast reduces seizures in pentylenetetrazol-kindled mice

Cysteinyl leukotrienes (CysLTs) have been implicated in seizures and kindling; however, the effect of CysLT receptor antagonists on seizure frequency in kindled animals and changes in CysLT receptor expression after pentylenetetrazol (PTZ)-induced kindling have not been investigated. In this study, we evaluated whether the CysLT1 inverse agonist montelukast, and a classical anticonvulsant, phenobarbital, were able to reduce seizures in PTZ-kindled mice and alter CysLT receptor expression. Montelukast (10 mg/kg, sc) and phenobarbital (20 mg/kg, sc) increased the latency to generalized seizures in kindled mice. Montelukast increased CysLT1 immunoreactivity only in non-kindled, PTZ-challenged mice. Interestingly, PTZ challenge decreased CysLT2 immunoreactivity only in kindled mice. CysLT1 antagonists appear to emerge as a promising adjunctive treatment for refractory seizures. Nevertheless, additional studies are necessary to evaluate the clinical implications of this research.

Electrocorticogram and behavior of electrically kindled epileptic rats / 中国比较医学杂志

Objective The current study was aimed to establish an electrically amygdala kindling model of refractory epilepsy in Sprague-Dawley rats, and to study their changes of electrocorticagram ( ECoG ) .Materials and methods Male Sprague-Dawley rats were used in the experiment.Two-polar electrode was implanted into the right amygdala stereotactically.Two weeks after the surgery, electrical stimulations were given to elicit the grade 4 seizure in all animals with the fast kindling protocol.Rekindling was administrated after the first kindling.The after discharge threshold ( ADT) and the number of stimulus were reassessed in the two kindling protocols.ECoG and the behavior of the animals were recorded during the whole experiment.Result The changes of ECoG and behavior: Animals showed stage 1 -3 seizure when the ADT was assessed.While during the kindling period, the animals showed generalized convulsion with stage 4-5 seizure.ECoG showed sharp waves, spike waves, sharp-slow waves and spike-slow waves.Statistical analysis showed that the ADT was not significantly increased at two weeks after kindling ( from 83.33 ±22.29μA to 84.17 ±16.76μA, P=0.923 ) .The number of stimulus given to elicit the stage 4 convulsion was not significantly increased as well ( from 4.41 ±2.27 to 5.58 ±3.96, P=0.231 ) .Conclusions Rapid kindling model of epilepsy in rats is an effective epilepsy model, which is stable for 2 weeks.

Synaptic vesicle protein2A decreases in amygdaloid-kindling pharmcoresistant epileptic rats / 华中科技大学学报（医学）（英德文版）

Synaptic vesicle protein 2A (SV2A) involvement has been reported in the animal models of epilepsy and in human intractable epilepsy. The difference between pharmacosensitive epilepsy and pharmacoresistant epilepsy remains poorly understood. The present study aimed to observe the hippocampus SV2A protein expression in amygdale-kindling pharmacoresistant epileptic rats. The pharmacosensitive epileptic rats served as control. Amygdaloid-kindling model of epilepsy was established in 100 healthy adult male Sprague-Dawley rats. The kindled rat model of epilepsy was used to select pharmacoresistance by testing their seizure response to phenytoin and phenobarbital. The selected pharmacoresistant rats were assigned to a pharmacoresistant epileptic group (PRE group). Another 12 pharmacosensitive epileptic rats (PSE group) served as control. Immunohistochemistry, real-time PCR and Western blotting were used to determine SV2A expression in the hippocampus tissue samples from both the PRE and the PSE rats. Immunohistochemistry staining showed that SV2A was mainly accumulated in the cytoplasm of the neurons, as well as along their dendrites throughout all subfields of the hippocampus. Immunoreactive staining level of SV2A-positive cells was 0.483 ± 0.304 in the PRE group and 0.866 ± 0.090 in the PSE group (P < 0.05). Real-time PCR analysis demonstrated that 2(-ΔΔCt) value of SV2A mRNA was 0.30 ± 0.43 in the PRE group and 0.76 ± 0.18 in the PSE group (P < 0.05). Western blotting analysis obtained the similar findings (0.27 ± 0.21 versus 1.12 ± 0.21, P < 0.05). PRE rats displayed a significant decrease of SV2A in the brain. SV2A may be associated with the pathogenesis of intractable epilepsy of the amygdaloid-kindling rats.

Role of piracetam on cognitive function in epilepsy and with antiepileptics in rats.

Background: To study extent of cognitive impairment by epilepsy & antiepileptic treatment and evaluate the role of piracetam on it. Methods: 48 animals were divided into 6 groups: I-Control, II- Topiramate, III-Topiramate+Piracetam, IV-Valproate, V-Valproate+Piracetam, VI-Piracetam. Baseline cognitive functions were measured using Cook’s pole climbing apparatus (CPCA) and Elevated plus maze (EPM). In CPCA, on completion of training, number of avoidances (NOA) out of 10 trials were noted while in EPM, transfer latency (TL) was measured. Kindling was induced by 30mg/kg Pentylenetetrazol (PTZ), i.p. to all groups (except Group I) on alternate days till seizures developed. Groups were treated with respective drugs orally for 21 days and cognitive functions measured again. Results: Significant decrease in NOA & increase in TL was observed after PTZ kindling. Topiramate further significantly impaired NOA and TL whereas Valproate significantly reduced NOA in CPCA but increase in TL was not significant. Treatment with Piracetam significantly increased Topiramate, Valproate and PTZ kindling induced decrease in NOA as also significantly reduced Topiramate and PTZ kindling induced increase in TL. Conclusion: Seizures are associated with cognitive impairment. Cognitive impairment caused by Sodium valproate differs from Topiramate. Piracetam, a known nootropic can be used in alleviating cognitive impairment associated with epilepsy & chronic antiepileptic therapy.

Antiepileptogenic and Anticonvulsant Actions of Dalbergia saxatilis (Hook, F.) in Sub-toxic Chemical Kindling and Toxic Convulsant Models.

Aims: The aqueous root extract of Dalbergia saxatilis (DS) is used in traditional African medicine to manage convulsions and epilepsies. This study aimed at investigating DS action against models that mimic seizure development in the neurons of epileptics, the sub-toxic dose kindling models. Study Design: Sub-toxic doses of strychnine and picrotoxin chemical kindling models; as well as single-dose toxic bicuculline convulsive models in mice. Place and Duration of Study: Neuropharmacology Unit Laboratory, Department of Pharmacology, College of Medicine, University of Lagos, Lagos, Nigeria, between July 2006 and March 2008. Methodology: Strychnine kindling was produced by a 48h interval, i.m administration of 1.5mg/kg strychnine for 9 trials. The mice were treated with 200mg/kg, p.o. DS, before strychnine thus: Group I: throughout the 1st - 9th kindling; group II: During the 1st - 5th kindling; and group III: during the 6th - 9th kindling trials. Control group received distilled water instead of DS throughout the 1st - 9th kindling trials. For picrotoxin study, a subconvulsant dose of 1.5mg/kg picrotoxin was injected i.p. 3 times a week for 10 weeks, 200mg/kg of DS was administered orally before picrotoxin thus: Group I: throughout the 1st - 30th kindling trials; group II: during the 1st - 12th kindling trials; group III: during the 13th - 30th kindling trials; control group received distilled water instead of DS throughout the 30 trials. Behavioural seizures were classified for seizure stages. In another study, DS (50- 200 mg/kg, p.o.) was administered to mice, 30 min. before 10mg/kg, s.c. bicuculline and onset to seizures and time to death noted. Results: DS significantly (P=.05) retarded the development and progression of strychnine kindling, but did not reverse already reached kindled state. Moreover, DS significantly (P=.05) retarded the development of picrotoxin kindling, decreased the scoring from kindling progression and prevented convulsion in fully picrotoxin-kindled mice. A significant delay of seizure onset, with complete protection at 200mg/kg DS was produced against bicuculline seizures in mice. Conclusion: DS may attenuate development of seizures in both GABAergic and glycinergic mechanisms and be useful in the prevention of seizures as well as neuroprotection in epileptics, justifying its use in the folkloric management of epilepsies.

Decreased expression of γ-aminobutyric acid receptor in the hippocampal tissues of pharmacoresistant temporal lobe epileptic rats / 中华神经科杂志

Objective To establish a multi-drug resistant model of temporal lobe epilepsy,and to observe the changes of γ-aminobutyric acid (GABA) receptor expression in the hippocampal tissues so as to explore its effects in pharmacoresistant epileptogenesis.Methods One hundred rats were selected to prepare the amygdaloid kindled model of epilepsy by chronic stimulation of amygaloid basal lateral nucleus.After the kindled model of epilepsy was prepared successfully(n =52),pharmacoresistant epileptic rats were selected according to their response to the phenobabital and phenytoin.The selected pharmacoresistant epileptic rats (n =8)were sacrificed and the hippocampus was removed to determine the GABA receptor expression,and the same number of pharmacosensitive epileptic rats was used as control.Results The pharmacoresistant epileptic rats displayed degenerative and necrotic hippocampal neurons.The arrangement of hippocampal neurons was disordered,and the structural characteristics of the arrangement of the hippocampal neurons disappeared.The gray values of GABAA-positive neurons in the hippocampal tissues (141.15 ± 14.72) increased significantly compared with the pharmacosensitive epileptic rats (92.56 ± 5.17; t =3.380,P =0.006).Western blot method demonstrated that the band of GABAA became narrowed and thin.The relative quantity of GABAA in the hippocampal tissues (0.38 ± 0.08) decreased significantly as compared with the pharmacosensitive epileptic rats (0.88 ± 0.18).A significant difference was observed (t =5.420,P =0.002).Conclusions GABA receptor expression might be decreased in the hippocampal tissues of pharmacoresistant epileptic rats.It might play a certain role in the formation of pharnmacoresistant epilepsy.

Effect of hippocampal electrical stimulation on the sodium channel current in CA1 region neurons in rats with pharmacoresistant temporal lobe epilepsy / 中华神经科杂志

Objective To establish a multi-drug resistant model of temporal lobe epilepsy,and then the sodium current of pyramidal neurons in CA1 areas of the hippocampus was used as as index to observe the effect of hippocampal stimulation on pharmacoresistant epileptic rats.Methods Eighty Wistar rats were selected to prepare an amygdaloid kindled model of epilepsy by chronic stimulation of amygaloid basal lateral nucleus.When the kindled model of epilepsy was prepared successfully,the pharmacoresistant epileptic rats were selected according their response to phenobabital and phenytoin.The selected pharmacoresistant epileptic rats were divided into a hippocampal stimulation group (HS group) and a pharmacoresistant control group (PR group).A low-frequency hippocampal stimulation was performed in the HS group,while the PR group received sham stimulation.The whole-cell recording technique by patch-clamp was used to observe the changes of sodium current of hippocampal pyramidal neurons after the hippocampal stimulation.Results Compared with the PR group,the pharmacoresistant epileptic rats in HS group underwent low-frequency stimulation for 2 weeks showed that the amygdale stimulus-induced seizures were decreased (2.32 ± 0.38 in HS group and 4.45 ± 0.42 in PR group,t =84.600,P =0.000) and the parameters of the after-discharges were improved significantly.In HS group,the peak current shifted towards depolarization,the sodium channels were difficult to activate,and were more susceptible to inactivation.Moreover,the recovery time after the sodium channel inactivation was slower in HS group ((17.9 ±0.6) s) than in PR group((16.3 +0.3) s,t =-25.420,P =0.000).Conclusions Hippocampal stimulation may inhibit the sodium channel current of pyramidal neurons in CA1 areas of hippocampus.The mechanism of hippocampal stimulation in the treatment of pharmacoresistant epilepsy might be achieved partly by inhibiting the sodium channel current so as to decrease the excitability of hippocampal neurons.

Effects of the Aqueous Extract of Anethum graveolens Leaves on Seizure Induced by Pentylenetetrazole in Mice

Background: In this study, the aqueous extract of Anethum graveolens (dill) leaves was studied for its effects on treating convulsions and epilepsy, by using a pentylenetetrazole (PTZ) kindling model. The evaluated plant has a traditional medical reputation for profound anticonvulsant activities, additionally, dill has been claimed to exhibit anti-inflammatory and analgesic properties. Methods: For the PTZ kindling induction, mice were given a dose of PTZ (37 mg/kg, intraperitoneally) every other day, and seizure stages were precisely recorded. During and after kindling, the effects of the non-toxic doses of the aqueous extracts (100, 250, and 400 mg/kg) on seizure latency in stage 2 (S2L), seizure latency in stage 4 (S4L), and seizure duration in stage 5 (S5D) were measured. Results: The aqueous extract of dill leaves had a noticeable anticonvulsant effect. The 400 mg/kg dose of the extract sample decreased with S5D (P < 0.05), and increased with S2L and S4L significantly (P < 0.05 and P < 0.01, respectively). Conclusion: The obtained data shows that the aqueous extract possesses anticonvulsant activity against seizure induced by PTZ. The presence of anticonvulsant compounds in this medicinal herb suggests further activity and guided fractionation studies in order to introduce this plant as a valuable source of anticonvulsant agents.

Effect of Adenosine A2A Receptor Antagonist ZM241385 on Amygdala-kindled Seizures and Progression of Amygdala Kindling / 华中科技大学学报（医学）（英德文版）

The purpose of this study was to evaluate the effect of adenosine A2A receptor antagonist ZM241385 on amygdala-kindled seizures and its roles in epileptogenesis.Electrodes were implanted into the right amygdala of male adult Wistar rats.Kindling was accomplished by using stimulus strength of 500 μA applied daily to the amygdala until 10 consecutive stage 5 seizues were induced.Then effect of ZM241385 was studied in fully kindled rats after intracerebroventricular administration of the drug.In addition,the effect on kindling progression was evaluated through ZM241385 injection before daily stimulation.In all experiments,behavioral changes in the rats in response to ZM241385 were monitored closely.The results showed that,in fully amygdala-kindled rats,ZM241385 (0.001-.1 nmol/L) decreased afterdischage duration (ADD),motor seizure duration (MSD),stage 5 duration (S5D) and seizure duration (SD),but only the effect on ADD was dose-dependent.The doses of 0.001-0.1 nmol/L had no influence on stage 4 latency (S4L) and seizure stage (SS).The dosages of 0.0001 and 1 nmol/L of ZM241385 did not exert any effect on all seizure parameters.In contrast to the results in fully amygdala-kindled rats,ZM241385 (0.001-0.1 nmol/L) had minimal or no effects on the progression of amygdala-kindled seizures.We are led to the conclusion that although ZM241385 had no influence on the progression of amygdala-kindled seizures,it had potent anti-convulsant profile and little adverse effects at the dosage of 0.001-0.1 nmol/L,suggesting that the agent is effective against the amygdala-kindled seizures.

Anticonvulsant evaluation of Rauvolfia ligustrina Willd. ex Roem. & Schult., Apocynaceae, in rodents / Avaliação anticonvulsivante de Rauvolfia ligustrina Willd. ex Roem. & Schult., Apocynaceae, em roedores

The Aim of this study was to evaluated the effects of the ethanol extract of Rauvolfia ligustrina Willd. ex Roem. & Schult., Apocynaceae, roots (EER) in animal models of epilepsy. The EER increased the latency for convulsions significantly different from control (p<0,05) and in the PTZ induced convulsions test on 62,5 mg/kg (i.p.) decreased mortality. This effect was blocked by flumazenil administration, suggesting an involvement of GABAergic system in the anticonvulsant activity of EER. The EER had a moderate effect only against PIC- or STR-induced convulsions at doses 125 and 250 mg/kg. But in the MES test it did not demonstrate effect on this animal model. Therefore, the EER reduced the development of PTZ-induced kindling in both experimental groups. It also significantly (p<0.05) decreased the latency for convulsions and reduced its percentage. Our results suggest that EER owns anticonvulsant property.

O presente estudo buscou avaliar os efeitos do extrato etanólico das raízes de Rauvolfia ligustrina Willd. ex Roem. & Schult., Apocynaceae, (EER) e sua possível atividade anticonvulsivante em roedores. No teste das convulsões induzidas pelo pentilenotetrazol (PTZ) os animais tratados com EER, 250 mg/kg (i.p.), apresentaram aumento significativo (p<0,05) da latência para o aparecimento das convulsões (328,9±47,5) quando comparado aos do grupo controle (103,5±21,8) e reduziu o número de óbitos. Esse efeito foi bloqueado pela administração do flumazenil. O EER produziu aumento significativo (p<0,05) na latência nos testes da picrotoxina (PIC) e da estricnina (EST), nas maiores doses. No modelo do eletrochoque auricular o EER não produziu alterações significativas em nenhum dos parâmetros avaliados. Entretanto, no modelo do abrasamento induzido pelo PTZ, a administração com o EER produziu um efeito protetor, atenuando de forma significativa (p<0,05) o desenvolvimento e a severidade das crises convulsivas. Os resultados, sugerem que o EER induziu efeito anticonvulsivante em roedores e que o sistema GABAérgico pode estar envolvido nessa resposta.

Comparison of different effects of electric stimulation of vagus nerve,peripheral nerve,and motor cortex on pentylenetetrazol induced convulsion in rats / 中华神经科杂志

Objective To investigate whether there are different effects of electric stimulation of vagus nerve,peripheral nerve(sciatic nerve and trigeminal nerve),and motor cortex on pentylenetetrazol (PTZ)induced convulsion in rats.Methods The vagus nerve and sciatic nerve were exposed in rats.The stimulation electrodes were placed on the vagus nerve,sciatic nerve,trigeminal nerve,and motor cortex,respectively.After electric stimulation,PTZ(50 mg/kg)was intraperitoneally injected into the rats.The pattern and latency of the convulsion seizure were observed and recorded.Results Racine's grade Ⅰ-Ⅴ grade convulsion seizure Was present in 9 rats(9/10)in the control group after the injection of PTZ.However,this intensity Was reduced to Ⅰ-Ⅲ grade differentially in all the rats by electric stimulation of the vagus nerve(5/10)or peripheral nerve(6/10 and 5/10).Furthermore,in the group of rats stimulated at motor cortex,there Was completely no convulsion.On the other hand,when pathological changes appeared in cortex or hippocampus(i.e.epileptic model was set up by 7 weeks stimulation),the same stimulation of motor cortex was not able to inhibit the convulsion seizure induced by injection of PTZ and all these rats showed Ⅳ-Ⅴ grade seizure(10/10).Conclusions In physiological condition,all of the four types of stimulation differentially reduced intensity of convulsion seizure triggered by PIZ injection and motor cortex stimulation has the best effect.However.when rats were in pathological status and epileptic nidus appeared in their brains.stimulatiion of motor cortex has no effect on PTZ induced convulsion seizure.

Improvement in hippocampal kindling analysis through computational processing data / Aprimorando a análise do modelo de kindling hipocampal com o auxílio de processamento computacional

The kindling phenomenon is classically investigated in epileptology research. The present study aims to provide further information about hippocampal kindling through computational processing data. Adult Wistar rats were implanted with dorsal hippocampal and frontal neocortical electrodes to perform the experiment. The processing data was obtained using the Spike2 and Matlab softwares. An inverse relationship between the number of "wet dog shakes" and the Racine's motor stages development was found. Moreover it was observed a significant increase in the afterdischarge (AD) duration and its frequency content. The highest frequencies were, however, only reached at the beginning of behavioral seizures. During the primary AD, fast transients (ripples) were registered in both hippocampi superimposed to slower waves. This experiment highlights the usefulness of computational processing applied to animal models of temporal lobe epilepsy and supports a relevant role of the high frequency discharges in temporal epileptogenesis.

O fenômeno de kindling é classicamente utilizado no campo da epileptologia experimental. Este trabalho objetiva aprofundar a análise do modelo kindling hipocampal através de processamento computacional. Ratos wistar adultos receberam eletrodos hipocampais dorsais e neocorticais frontais para a realização do experimento. O processamento dos dados encontrados foi realizado pelos softwares Matlab e Spike2. Encontrou-se uma relação inversa entre wet dog shakes e o desenvolvimento dos estágios motores de Racine. A duração e o conteúdo de freqüência das pós-descargas hipocampais aumentaram durante o processo, sendo observadas descargas de alta freqüência (ripples) em ambos os hipocampos durante as pós-descargas primárias, superimpostas a ondas lentas. As mais altas freqüências, entretanto, foram apenas atingidas com o início das crises epilépticas. A utilização de sistemas computacionais para a confecção e análise do modelo de epilepsia temporal é ressaltada e reforça-se a relevância do papel das altas freqüências na epileptogênese temporal.

The dynamic changes of adenosine receptors imbalance during kindling by lithium chloride-pilocarpine / 中华神经科杂志

Objective To investigate the dynamic changes of adenosine receptors, A1 (A1R) and A2a (A2aR) in the brain from the acute to chronic phase after kindling and to explore the correlation between seizure and expression level of A1R and A2aR. MethodsRats were randomly selected into the testing model, reference and normal control groups.Testing rats were kindled by lithium choride-pilocarpine, reference rats were treated with saline, and no treatment was given in normal control group. The dynamic expression of A1R and A2aR were detected by RT-PCR, immunofluorescence staining and Western blot at time-points of 24 hours, 1 month and 6 months post-kindling. Results In the acute phase of 24 hours after kindling, the A1R expression level (mRNA level was (1. 1483 ±0. 1182); Western blot result was ( 0. 7872± 0. 0621 ) ; immunofluorescence staining count was ( 76. 17 ± 4. 62 )/HP) was increased and A2aR (mRNA level was (0. 8338±0. 0572) ; Western blot result was (0. 2098 ±0. 0257) ; immunofluorescence staining count was (43. 83 ± 5. 12 )/HP) was decreased.The results showed statistically difference compared with the reference and normal groups (P< 0. 05 ). In the later chronic phase of 1 month and 6 months after kindling, the expression level of A1R was decreased and A2aR was increased. These data revealed statistically significant difference (P <0. 01 ). Furthermore, the comparison of the results in 1 month and 6 months after kindling found that the expression of AIR was lower in 6 months (mRNA level was (0. 5682 ±0. 0443) ; Western blot result was (0. 7749 ±0. 0262) ; immunofluorescence staining count was (38. 50 ±4. 81 )/HP) than in 1 month and that of A2aR was higher in 6 months (mRNA level was (1. 2169±0. 0332) ; Western blot result was (0. 7080 ±0. 0371 ); immunofluorescence staining count was (114. 50 ± 4. 04)/HP). The differences were statistical significant (t = - 19. 02--13.28, P < 0. 05). ConclusionsThe expressions of A1R and A2AR during and after kindling presents a bidirectional change. In the acute phas the expression of AR is regulated to suppress seizures. While in the chronic phase, the repeated seizures result in the change of A1R and A2aR expression in the opposite direction. This mechanism plays an important role in refractory seizures.