Metabolomics Analysis of Chloriti Lapis on Brain Tissue of PTZ-kindled Epileptic Rats / 中国实验方剂学杂志

Objective:To explore the possible mechanism of Chloriti Lapis in the treatment of epilepsy by the metabonomics of brain tissue in pentylenetetrazol （PTZ）-kindled epileptic rats treated with Chloriti Lapis. Method:The epileptic animal model in rats was established by PTZ kindling， and the rats were divided into the control group， model group， carbamazepine group and Chloriti Lapis group. The brain tissue samples were detected by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry（UPLC/Q-TOF-MS）， and the experimental results were statistically analyzed by partial least squares-discriminant analysis （PLS-DA） and SPSS 18.0. Result:The metabolic fingerprints and metabolic profiles of the rat brain tissue were established， which showed that the metabolic profiles of each group had changed significantly and could be separated well among the groups. Moreover， the Chloriti Lapis group had a tendency to be closer to the control group than the carbamazepine group. Seven differential metabolites were screened， including phosphatidylserine （PS） （18∶0/18∶0）， <italic>L</italic>-glutamic acid， docosahexaenoyl ethanolamide， arachidonic acid， glucosylsphingosine， cholestane-3，7，12，24，25-pentol and lysophosphatidylcholine （LysoPC） （P-18∶0）. Except for docosahexaenoyl ethanolamide and LysoPC （P-18∶0）， Chloriti Lapis had significant intervening and regulating effects on the other five differential metabolites. There were 12 possible metabolic pathways that affected the metabolic disorder of PTZ-kindled rats， and 3 important metabolic pathways （pathway impact>0.1）， namely， <italic>D-</italic>glutamine and <italic>D-</italic>glutamate metabolism， alanine， aspartate and glutamate metabolism， and arachidonic acid metabolism， among which <italic>D-</italic>glutamine and <italic>D-</italic>glutamate metabolism was the most important metabolic pathways. Conclusion:From this point of view， Chloriti Lapis has a clear intervention effect on PTZ-kindled epileptic rats， which may be related to the intervention of the above differential metabolite contents and related metabolic pathways. It can reduce the toxic effect of excitatory neurotransmitters on neurons in brain tissue and inhibit the development of inflammation in brain tissue， so as to maintain the biological function of brain cells and slow down the occurrence of epilepsy.

Effect of Chloriti Lapis on Metal Elements in Brain and Plasma of PTZ-kindled Epileptic Rats / 中国实验方剂学杂志

Objective:To investigate the effect of Chloriti Lapis on metal elements in brain tissue and plasma of epileptic rats kindled by pentylenetetrazol （PTZ）， and to explore the possible material basis of Chloriti Lapis. Method:PTZ kindling method was used to establish epileptic rat model. Inductively coupled plasma mass spectrometry （ICP-MS） and inductively coupled plasma optical emission spectrometer （ICP-OES） were used to determine the contents of metal elements in brain tissue and plasma of the blank group， model group， carbamazepine group （0.1 g·kg^-1） and Chloriti Lapis group （2 g·kg^-1）. The data were statistically analyzed by SPSS 18.0 software. Result:Compared with the blank group， the contents of Sr， Sb and Ba in brain tissue of rats in the model group were significantly increased （<italic>P</italic><0.05， <italic>P</italic><0.01）， while the contents of Zn， Fe， Cu， K， Li， Co， Sn and Pb were significantly decreased （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the model group， the contents of Zn， Fe， K， Li， Co， As and Pb in brain tissue of rats in the Chloriti Lapis group were obviously increased （<italic>P</italic><0.05， <italic>P</italic><0.01）， while the contents of Sr and Sb were significantly decreased （<italic>P</italic><0.01）. These results showed that Chloriti Lapis had positive effect on the regulation of the content of metal elements in rat brain tissue to normal level， the intervention effect was clear， and the overall effect was better than that of carbamazepine group. The determination of 21 metal elements in plasma showed that compared with the blank group， the levels of K， Sr and Cd in the model group were significantly increased （<italic>P</italic><0.05）， and the contents of Li， Al， Ti and Cr were significantly decreased （<italic>P</italic><0.05）. Compared with the model group， the contents of Ca， K， Li， Al and V in the Chloriti Lapis group were obviously increased （<italic>P</italic><0.05， <italic>P</italic><0.01）， and the contents of Fe， Ti， Sr and Cd were significantly decreased （<italic>P</italic><0.05，<italic>P</italic><0.01）. The correlation analysis of metal elements among the groups showed that there were 17 pairs of elements had positively correlation in the brain tissue of rats， 2 pairs of elements had significant negative correlation. In the plasma of rats， 8 pairs of elements had significant positive correlation and 6 pairs of elements had significant negative correlation. Conclusion:The metal element groups represented by Zn， Fe， K， Li， Co， As， Pb， Sr， Sb， Ca， Al， V， Ti and Cd may be the effective material basis for Chloriti Lapis to interfere PTZ-kindled epileptic model rats， which may be related to the influence of these metal element groups on the release of neurotransmitters and the electrical balance of neurons， the regulation of abnormal synchronous discharge induced by Na⁺， K⁺， Ca²⁺ channel disorders and intervention of metabolism pathways in brain tissue related to epilepsy. It can make the excitatory and inhibitory activities restrain each other， and finally reach the normal physiological state of neurons and cells. The intervention effect of Chloriti Lapis group was better than that of carbamazepine group.

SAD-B modulates epileptic seizure by regulating AMPA receptors in patients with temporal lobe epilepsy and in the PTZ-induced epileptic model

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are the predominant mediators of glutamate-induced excitatory neurotransmission. It is widely accepted that AMPA receptors are critical for the generation and spread of epileptic seizure activity. Dysfunction of AMPA receptors as a causal factor in patients with intractable epilepsy results in neurotransmission failure. Brain-specific serine/threonine-protein kinase 1 (SAD-B), a serine-threonine kinase specifically expressed in the brain, has been shown to regulate AMPA receptor-mediated neurotransmission through a presynaptic mechanism. In cultured rat hippocampal neurons, the overexpression of SAD-B significantly increases the frequency of miniature excitatory postsynaptic currents (mEPSCs). Here, we showed that SAD-B downregulation exerted antiepileptic activity by regulating AMPA receptors in patients with temporal lobe epilepsy (TLE) and in the pentylenetetrazol (PTZ)-induced epileptic model. We first used immunoblotting and immunohistochemistry analysis to demonstrate that SAD-B expression was increased in the epileptic rat brain. Subsequently, to explore the function of SAD-B in epilepsy, we used siRNA to knock down SAD-B protein and observed behavior after PTZ-induced seizures. We found that SAD-B downregulation attenuated seizure severity and susceptibility in the PTZ-induced epileptic model. Furthermore, we showed that the antiepileptic effect of SAD-B downregulation on PTZ-induced seizure was abolished by CNQX (an AMPA receptor inhibitor), suggesting that SAD-B modulated epileptic seizure by regulating AMPA receptors in the brain. Taken together, these findings suggest that SAD-B may be a potential and novel therapeutic target to limit epileptic seizures.

Evaluation Of Anticonvulsant Activity Of Cow Urine Betel Vine Extract In Mice

The present study was designed to investigate the anticonvulsant activity of Cowurine betel vine extract in rats. Anticonvulsant activity was performed by using the two modelsMaximal Electric Shock (MES) induced convulsions and Pentylene tetrazole (PTZ) inducedconvulsions. The animals were fed with Cow urine betel vine extract at the dose of 250 and500mg/kg b.w orally for a period of 14 days. The pretreated extract reduced the convulsions ina dose dependent manner which was determined by taking the duration of flexion, extensor,clonus and stupor phase and Percentage of inhibition of seizures relative to controls wascalculated.

Anticonvulsant activity of Adhatoda vasica leaves by pentylenetetrazol model: preliminary evaluation in rats

Background: Epilepsy is a disorder characterised by recurrent seizures of cerebral origin with episodes of sensory, motor phenomenon with or without loss of consciousness. The present study was taken up to evaluate the anticonvulsant effect of aqueous extract of leaves of Adhatoda vasica in rats. Objectives of this study is to evaluate the effect of aqueous extract of Adhatoda vasica leaves on Pentylenetetrazol induced seizures in albino rats and to compare the effect of aqueous extract of Adhatoda vasica leaves with standard dose of sodium valproate on Pentylenetetrazol induced seizures in albino rats.Methods: Anticonvulsant activity of aqueous extract of Adhatoda vasica was analysed using PTZ (Pentylenetetrazol) model. Groups used were distilled water as control group, Sodium valproate as standard for Pentylenetetrazol and two doses of aqueous extract of Adhatoda vasica (100mg/kg and 200 mg/kg) for this screening model. Parameters observed for PTZ models were abolition of clonic seizures and time duration between injection of PTZ and onset of seizures.Results: In PTZ model, test group at 200 mg/kg showed 33.33% protection for abolition of clonic seizures, though not comparable to standard group. There was significant increase in the duration of onset of clonic seizures after PTZ injection in both test groups (at 100 mg/kg and 200 mg/kg) when compared to control group.Conclusions: Aqueous extract of leaves of Adhatoda vasica has shown significant anticonvulsant action in PTZ model.

Effect of calcium channel blocker as anticonvulsant and its potentiating effect when used along with sodium valproate in pentylenetetrazole induced seizures in Albino rats

Background: Many antiepileptic drugs were introduced for the treatment of epilepsy. Ideal antiepileptic drug should not only prevent but also correct the underlying pathophysiology without altering the normal neurotransmission. Calcium channel blockers may form such group because initiation of seizure is associated intrinsic burst firing which is triggered by large inward calcium current, so this study was done to evaluate the anticonvulsant effect of amlodipine in albino rats.Methods: A total of 42 adult albino rats were included in the study and divided into 7 groups, each containing 6 rats. Group 1 received distilled water, group 2,3 received sodium valproate 50mg/kg and 100mg/kg, group 4-6 received amlodipine 1, 2, 4mg/kg and group 7 received combination of Amlodipine 1 mg/kg and sodium valproate 50mg/kg. Pentylenetetrazole induced seizures model was done and onset of myoclonic jerks, onset of clonic convulsions and duration of clonic convulsions was studied.Results: There was a significant anticonvulsant effect in Amlodipine doses 2, 4mg/kg (p <0.001). The combination of Amlodipine (1mg/kg) and Sodium valproate (50mg/kg) also had significant anticonvulsant effect.Conclusions: Amlodipine, a calcium channel blocker has anticonvulsant effect and also potentiated the anticonvulsant effect of low dose sodium valproate.

Evaluation of antiepileptic activity of trachyspermum ammi (ajwain oil) alone and as an adjuvant to diazepam in swiss albino mice

Background: Epilepsy is defined as a group of chronic neurological disorders characterized by recurrent and unprovoked seizures. Taking into account high prevalence of epilepsy and the adverse effects of the current antiepileptic agents which leads to noncompliance, more attempts should be made to re-explore the natural sources for new drug discoveries.Methods: The antiepileptic activity of Ajwain oil alone and as adjuvant to diazepam in swiss albino mice was evaluated using Maximum Electro Shock (MES) and Pentylenetetrazole (PTZ) induced seizure model. A total of forty eight (N=48) swiss albino mice weighing 20-30g of either sex were used in the study. Animals were divided into 2 sets of 24 animals each, which were further divided into 4 groups of 6 animals each. In either set, control received - 2% Tween 80 (10mg/kg); standard- Diazepam (2mg/kg); Test drug- Ajwain oil (75mg/kg) and Adjuvant group- Ajwain oil (75mg/kg) + Diazepam (2mg/kg). All the drugs were given intraperitoneally 30min before inducing seizures.Results: One way ANOVA was used to compare the means of all the groups followed by post Hoc Tukey’s test for statistical evaluation. In MES model, test drug showed statistically significant antiepileptic activity compared to control, however the results were comparable to standard. In PTZ, adjuvant therapy showed significant activity compared to standard, with a p value <0.001.Conclusions: Therefore, authors conclude that Ajwain oil has significant anti-epileptic activity.

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.

Panchagavya Ghrita, an Ayurvedic formulation attenuates seizures, cognitive impairment and oxidative stress in pentylenetetrazole induced seizures in rats.

Panchagavya Ghrita (PG), according to Ayurvedic formulary of India (AFI), is used to treat epilepsy (apasmara), fever (jvara), mania (unmade) and jaundice (kamala). In the present study, we examined its effect on convulsions, oxidative stress and cognitive impairment in pentylenetetrazole (PTZ) induced seizures in rats. PG @ 250, 500, 1000, 2000 and 4000 mg/kg was administered orally for 7 days to male Wistar rats. On day 7, PTZ (60 mg/kg) was injected intraperitoneally 2 h after the last dose of PG. Sodium valproate (300 mg/kg) was used as positive control. Latency to myoclonic jerks, clonus and generalized tonic clonic seizures (GTCS) were recorded for seizure severity. Cognitive impairment was assessed using elevated plus maze and passive avoidance tests. Malondialdehyde and reduced glutathione levels were measured in rat brain. The results have shown that pretreatment with PG @ 500, 1000, 2000 and 4000 mg/kg exhibited 16.6, 33.3, 50 and 100% protection against occurrence of GTCS. The pretreatment with PG has significantly improved cognitive functions and the oxidative stress induced by seizures demonstrating its protective effect against PTZ induced seizures, and further, use of PG as an anticonvulsant in Ayurvedic system of medicine.

To study the oxidative stress induced by lindane in epileptic rats brains and their modulation by neurosteroids.

Background: Lindane is pesticide has been shown to affect the nervous system adversely. Previous work has shown that lindane is proconvulsant and neurosteroids (NS) has been shown to be neuroprotective against lindane-induced convulsions. As the mechanisms of lindane in epileptogenesis is not completely understood. The present study was designed to investigate the oxidative stress parameters of lindane toxicity in epileptogenesis and their modulation by NS like allopregnanolone (AP), and 4ʹ-chlorodiazepam (4ʹ-CD) in pentylenetetrazole (PTZ) kindling methods. Methods: Kindling was induced by injecting PTZ (30 mg/kg; s.c.) on alternate days i.e., 3 times in a week. Lindane was also administered (15 mg/kg p.o) on alternate days for 6 weeks. AP (2.5 mg/kg, intaperitoneal [i.p.]) and 4ʹ-CD (0.5 mg/kg, i.p.) single dose was given in kindled rats before lindane. Results: Following per oral administration of lindane for 6 weeks produced signifi cant oxidative stress in epileptic brain. There was an increase in brain malondialdehyde (MDA) level and decrease in reduced glutathione (GSH) levels. AP (2.5 mg/kg, i.p.) and 4ʹ-CD (0.5 mg/kg, i.p.) single dose administration were not able to reverse the effect of chronic exposure of lindane. Conclusion: The result of the present study provides evidence that oxidative stress produced in the brain after chronic exposure of lindane may be the mechanism of epileptogenesis. Though NS have been shown to be neuroprotective, but they failed to reverse chronic oxidative stress produced by lindane. Further studies are required to demonstrate interaction of NS with lindane in oxidative stress.

Estudio fitoquímico cualitativo, actividad anticonvulsivante del extracto acuoso de las partes aéreas de Barberis boliviana lechler (Ch'eqche) en un modelo experimental inducido químicamente por por pentilentetrazol en animales de experimentación / Qualitative phytochemical study, anticonvulsant activity of the aqueous extract of the aerial parts of Barberis boliviana lechler (Ch'eqche) in an experimental model chemically induced by pentylenetetrazole in experimental animals

El uso de plantas para el tratamiento de las convulsiones es amplia en diversas culturas, pero en muchos casos no se cuenta con un respaldo científico, es el propósito de la presente investigación realizar el análisis frtoquímico cualitativo, la evaluación de la actividad anticonvulsivante y toxicidad aguda del extracto acuoso de las partes aéreas de Berberís boliviana L. "Ch'eqche" en animales de experimentación. Para evaluar la actividad anticonvulsivante se empleó el modelo de convulsión química inducida por pentilentetrazol (PTZ 85 mglkg v.i.p.), usando como metodología un cuasiexperimental. Se utilizó 5 grupos de 6 ratones Bald/c/CNPB; grupo 1 (control), grupo 2 (diazepam 1mglkg) y grupo 3, 4, 5 (400, 800 y 1200 mg/kg de extracto acuoso). El tratamiento fue por v.i.p 30 minutos antes de la inducción de las convulsiones. Se midió el período de latencia para la primera convulsión clónica, la duración de las convulsiones, número de convulsiones que duran por lo menos 3 segundos y la protección frente a la mortalidad. Para la prueba de toxicidad aguda por v.o se utilizaron 12 ratones albinos, para la primera fase a dosis de (10, 100 y 1000 mglkg de extracto acuoso) y 3 ratones por grupo, para la segunda fase a dosis de (1600, 2900 y 5000 mglkg de extracto acuoso) y un ratón por grupo. Resultados: Se evidenció la presencia de compuestos fenólicos, alcaloides, taninos, cumarinas, quinonas, lactonas, glicósidos, aminoácidos, saponinas, flavonoides y resinas. Se observó que los extracto acuoso de las partes aéreas de Berberís boliviana L.(Ch'eqche) a las dosis de 400, 800 y 1200 mg/kg incrementaron el período de latencia en 60,67%, 73,13% y 88,70%, disminuyeron la duración de las convulsiones en 21,85%, 45,23% y 52,22%, disminuyeron el número de convulsiones que duran por lo menos 3 segundos en 36,11%, 66,67% y 80,56%; con respecto al grupo control y la protección frente a la mortalidad fue de 33,3%, 50,0% y 100,0% (ANOVA p<0,05). El valor de la DL50 del extracto acuoso por el método de Lorke es mayor a 5000 mg/kg. Conclusiones: Se caracterizaron los metabolitos secundarios de la especie Berberís boliviana L. (Ch'eqche), se demostró la actividad anticonvulsivante a la dosis de 1200 mg/kg del extracto frente a convulsiones clónicas, presentando valores próximos al del diazepam y un 100% de protección frente a los efectos letales del agente convulsivante PTZ. La DL50 del extracto acuoso por vía oral es mayor a 5000 mg/kg.

Pharmacological justification for the ethnomedical use of Clausena anisata root-bark extract in the management of epilepsy.

Various morphological parts of the tropical plant, Clausena anisata (Wild) Hook [family: Rutaceae], have ethnomedical claim for use in the management of epilepsy. This study examined the antiepileptic activity of Clausena anisata root bark, stem bark and leaf ethanolic extracts (i.e. CARE, CASE and CALE respectively) against pentylenetetrazole (PTZ) induced seizures in mice. Phytochemical and acute toxicity tests were performed on the extracts followed by oral administration of graded doses of CASE (500, 750 and 1000 mg/kg), CARE and CALE (400, 600 and 800 mg/kg) to the mice, thirty minutes before the administration of PTZ (90 mg/kg i.p.). The anticonvulsant effect of the extracts and diazepam (4 mg/kg) were compared. CALE was found to possess large amount of saponins, CARE large amounts of tannins and saponins, CASE large amounts of flavonoids, alkaloids and tannins. While CARE at the dose level of 800 mg/kg significantly (p<0.05) delayed the onset of convulsions and afforded 33.33 % protection, neither CALE nor CASE could exert any significant protective effect on PTZ induced convulsions, whereas diazepam totally abolished the episodes of convulsions. This study suggests that the ethanolic root bark extract of Clausena anisata contains bioactive constituents that may be beneficial in petit mal epilepsy and lend pharmacological credence to the ethnomedical claim for the use of the plant in the management of epilepsy. Abbreviations: NMDA= N-methyl-D-aspartate, SCMC= sodium carboxy methyl cellulose, CARE= Clausena anisata root bark ethanolic extract, CASE= Clausena anisata stem bark ethanolic extract, CALE= Clausena anisata leaf ethanolic extract, PTZ= pentylenetetrazole.

The role of magnesium sulfate in prevention of seizures induced by pentylenetetrazole in rats / O papel do sulfato de magnésio na prevenção de crises induzidas por pentilenotetrazol em ratos

Magnesium sulfate (MgSO4) has been used to prevent seizures in eclampsia. This study examined the central effects of MgSO4 on different types of pentylenetetrazole (PTZ)-induced seizures. Male Wistar rats were submitted to intracerebroventricular (ICV) administration of MgSO4 at different doses followed by intraperitoneal administration of PTZ. The latency to the onset of the first seizure induced by PTZ was significantly increased by ICV administration of MgSO4 at a dose of 100 µg compared to the control treatment. In addition, the total period during which animals presented with seizures was significantly reduced at this dose of MgSO4. Furthermore, the latency to the onset of the first partial complex seizure was significantly increased by the lowest dose of MgSO4. However, a high dose of MgSO4 had no effect or even potentiated the effect of PTZ. These results suggest that, depending on the dose, MgSO4 may be important in prevention of epileptic seizures.

Sulfato de magnésio (MgSO4) é utilizado para prevenir crises epilépticas na eclampsia. Este estudo examina os efeitos do MgSO4 em diferentes tipos de crise induzidas por pentilenotetrazol (PTZ). Ratos Wistar foram submetidos à administração intracerebroventricular (ICV) de diferentes doses de MgSO4 seguida de administração intraperitoneal de PTZ. A latência para o início da primeira crise induzida por PTZ foi aumentada pela administração ICV de MgSO4 na dose de 100 µg quando comparada ao tratamento controle. Além disso, o período durante o qual os animais apresentaram crises foi reduzido com a mesma dose de MgSO4. A latência para o início da primeira crise parcial complexa também foi aumentada com a dose menor de MgSO4 (32 µg). No entanto, a maior dose (320 µg) de MgSO4 não foi efetiva ou até potencializou os efeitos do PTZ. Esses resultados sugerem que, dependendo da dose, o MgSO4 pode ser útil na prevenção de crises epilépticas.

Hydroalcoholic extract of Emblica officinalis Gaertn. affords protection against PTZ-induced seizures, oxidative stress and cognitive impairment in rats.

The cognitive impairment seen in epileptics may be a consequence of either the underlying epileptogenic process alone or it could manifest on account of the use of antiepileptic drugs that cause cognitive impairment as an adverse effect or both. Thus, there is a need for drugs that can suppress epileptogenesis without contributing to or , if possible, by acting to prevent the development of cognitive impairment. Emblica officinalis, an Indian medicinal plant, has marked antioxidant property. The effect of seven days pretreatment of 300, 500 and 700 mg/kg doses of hydroalcoholic extract of E. officinalis (HAEEO) administered intraperitoneally to rats was evaluated on pentylenetetrazole (PTZ) induced seizures, cognitive deficit and oxidative stress markers viz malondialdehyde (MDA) and glutathione. The 500 and 700 mg/kg ip doses of HAEEO completely abolished the generalized tonic seizures and also improved the retention latency in passive avoidance task. Further, HAEEO dose-dependently ameliorated the oxidative stress induced by PTZ. These findings suggest the potential of HAEEO to be used as an adjuvant to treatment with antiepileptic drugs.

Anticonvulsant activity of bacopa monniera in rodents / Anticonvulsivante atividade de bacopa monniera em roedores

Bacopa monnieri (L), belonging to the Scrophulariaceae family and commonly known as Brahmi, is well known in India for its CNS activity but its neuropharmacological effect has not yet been explored. In the present study, the antiepileptic effects of the plant were investigated. The ethanolic extract of Bacopa monniera was tested for anticonvulsant activity in albino rats, using different convulsive models. The ethanolic extract of leaves produced significant anticonvulsant activity for all the different models studied. The present study shows a probable mechanism of action similar to that of benzodiazepines (GABA agonist). Thus, these results emphasize the need to diversify by using alternative therapeutic approaches pertaining to herbal medicine, where a single easily available plant may provide solutions to several therapeutic challenges, as observed in the anticonvulsant action of ethanolic extract of B. monniera.

Bacopa monniera, da família Scrophulariaceae, e comumente denominada Brahmi, é bem conhecida na Índia por sua atividade no Sistema Nervoso Central, mas seu efeito neurofarmacológico não foi, ainda, explorado. No presente estudo, investigaram-se os efeitos antiepilépticos da planta. O extrato etanólico da Bacopa monniera foi testado quanto à atividade anticonvulsivante em ratos albinos, utilizando-se diferentes modelos de convulsão. O extrato etanólico das folhas produziu atividade anticonvulsivante significativa para todos os diferentes modelos estudados. O presente estudo mostra provável mecanismo de ação semelhante ao dos benzodiazepínicos (agonista do GABA). Assim sendo, esses resultados enfatizam a necessidade de diversificar, utilizando-se abordagens terapêuticas alternativas da medicina natural, em que uma planta facilmente disponível pode fornecer soluções para vários desafios terapêuticos, como o observado na ação anticonvulsivante do extrato etanólico de Bacopa monniera.

Anticonvulsant property of N-salicyloyltryptamine: evidence of enhance of central GABAergic neurotransmission / Propriedade anticonvulsivante de N-saliciloiltriptamina: proteção significativa com o sistema GABAérgico

AIM: In the present study we verified the anticonvulsant properties of the new tryptamine analogue, N-salicyloyltryptamine (NST), in rodents. METHODS AND RESULTS: In the evaluation of the anticonvulsant activity, NST protected the animals from the incidence of seizures induced by pentylenetetrazole (PTZ) and picrotoxin (PIC), in doses of 100 and 200 mg/kg. NST (100 and 200 mg/kg, i.p.) significantly eliminated the extensor reflex of maximal electric-induced seizure tests in 40 percent of the experimental animals. However, in the PTZ model FLU (10 mg/kg, i.p.), an antagonist of the benzodiazepine (BZD) site in the GABA A-BZD receptor complex, inhibited the prolongation of seizure latency induced by NST. CONCLUSION: Our results demonstrated an anticonvulsant activity of the new analogue that could be, at least in part, associated to the involvement of the GABAergic mechanism.

OBJETIVO: O presente estudo buscou avaliar o possível efeito anticonvulsivante do novo análogo da triptamina, N-saliciloiltriptamina (NST), em roedores. MÉTODOS E RESULTADOS: Na avaliação do efeito anticonvulsivante, os animais tratados com NST (100 e 200 mg/kg, i.p.) foram protegidos de maneira estatisticamente significativa (p<0,05) quanto a latência e incidência do aparecimento das convulsões induzidas pela administração do pentilenotetrazol (PTZ) e da picrotoxina (PIC). O efeito protetor do NST nas convulsões induzidas pelo PTZ foi revertido pela administração do flumazenil (10 mg/kg, i.p.), um antagonista dos receptores GABA-benzodiazepínicos (GABA A-BZD). A administração de NST (100 e 200 mg/kg, i.p.) protegeu de forma estatisticamente significativa (p < 0,05) os animais no teste das convulsões induzidas pelo eletrochoque-auricular em camundongos. CONCLUSÃO: Os resultados do presente estudo sugerem que o efeito anticonvulsivante de NST está associado, pelo menos em parte, ao sistema GABAérgico.

Susceptibility of Epilepsy in Rat with Cerebral Trauma / 中国康复理论与实践

@#Objective To explore the susceptibility of epilepsy in rat with cerebral trauma. Methods An impact-acceleration head injury model was established with rats. After trauma, the electroencephalograph was recorded. Epileptic model wad established by injecting pentylenetetrazol (PTZ) intraperitoneally and the dosage of PTZ was recorded. Results The wave of delta and theta increased after trauma, alpha and beta decreased and there was significant difference among the power of delta, theta and alpha (P＜0.05). The dosage of rats with cerebral trauma was less than that in normal rats (P＜0.05). Conclusion The susceptibility of epilepsy in rat with cerebral trauma increases.

Effect of Pingxian Powder on N-methyl-D-aspartate Recptor and ?-aminobutyric acid-A Receptor in the Temporal Cortex of Pentylenetetrazole Kindling Epileptic Rat Model / 中国中医药信息杂志

Objective To explore the possible antiepileptic mechanism of Pingxian Powder. Methods In the experiment,Pentylenetetrazole (PTZ) was injected into abdomen of rat to make epileptic kindling model. The total number,percentage of positive area and integral optical density of N-methyl-D-aspartate receptor1 (NMDAR1) and ?-aminobutyric acid-A receptor (GABA-AR?1) of immunoreactive cells in the temporal cortex were studied by the immunohistochemical method and image analyzing system. Results The total number,percentage of positive area and integral optical density of NMDAR1 of immunoreactive cells in the temporal cortex of model group were more than normal group (P

Interference effect of Kangxianzengzhi capsule on hippocampal mossy fiber sprouting in epileptic rat kindled by pentylenetetrazol / 中华中医药杂志

To explore the interference effect of Kangxianzengzhi(KXZZ) capsule on hippocampal mossy fiber sprouting in epileptic rat kindled by pentylenetetrazol.Methods: Epileptic rat models were established by pentylenetetrazol(PTZ) kindling method.All rats were divided into six groups: KXZZ high-does group,KXZZ middle-does group,KXZZ low-does group,valproate magnesium group, model group and normal group randomly.Then the hippocampal mossy fiber sprouting was monitored by Timm stain method.Results: Mossy fiber sprouting was obvious in the hippocampal CA3 section and the molecular layer of dentate syrus in model group.Compared with normal group,the percent of sprouting density in model group was higher(P

EEG alterations and conscious state of epileptic rats during absence seizure induced by pentylenetetrazol / 第三军医大学学报

Objective To evaluate whether the pentylenetetrazol(PTZ)model is an appropriate animal model of absence seizure.Methods A series of tests including EEG,active avoidance response(AAR)and passive escape response(PER)in a two-way shuttle box were finished during seizure induced by PTZ(35 mg/kg,ip)in 40 Wistar epileptic rats.Results Epileptiform activity was characterized by bilaterally spike wave discharges synchronously elicited during seizure in PTZ models.During absence seizure induced by PTZ,the latency of active avoidance response was significantly prolonged.AAR positive rate was decreased by 85%.PER positive rate was increased by 56%,and escape failure positive rate was increased by 29%.Conclusion There is epileptiform discharge accompanying transient conscious disturbance during absence seizure induced by pentylenetetrazol.