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1.
Braz. j. biol ; 83: 1-6, 2023. tab
Article in English | LILACS, VETINDEX | ID: biblio-1468878

ABSTRACT

Desvenlafaxine succinate (DVS) inhibits serotonin reuptake selectively and is approved for major depressive disorders. This research investigated influence of DVS on modulating brain monoamine and oxidative stress in mice. The antiepileptic potential of DVS (10, 20, or 30 mg/kg/i.p.) in pentylenetetrazole (PTZ; 85 mg/kg) with i.p. route of administration, strychnine (STR; 75 mg/kg) with i.p. route, pilocarpine (400 mg/kg) with s.c. route and maximal electroshock MES-induced convulsion in mouse models. The activities of oxidative stress, i.e. superoxide dismutase (SOD), glutathione (GSH) and lipid peroxidation (LPO) as well as gamma-aminobutyric acid (GABA) in the brains of PTZ-induced convulsive mice. Treatment with DVS increased the latency to develop siezures and declined mortalities in rodents against PTZ, STR and pilocarpine-induced convulsions. Results of MES-leaded siezures revealed that DVS reduced tonic hind limb extension duration and mortalities significantly. Brain, SOD, GSH and GABA level were significantly (P<0.01) increased and LPO reduced significantly (P<0.01) after DVS treatment. Furthermore, the DVS did not show any motor coordination signs in the rotarod test. We demonstrated that the role of DVS in convulsion genesis in mice under control condition and attenuate the PTZ-induced oxidative damage.


O succinato de desvenlafaxina (DVS) inibe seletivamente a recaptação da serotonina e é aprovado para transtornos depressivos maiores. Esta pesquisa investigou a influência do DVS na modulação da monoamina cerebral e do estresse oxidativo em camundongos. O potencial antiepiléptico de DVS (10, 20 ou 30 mg / kg / i.p.) Em pentilenotetrazole (PTZ; 85 mg / kg) com i.p. via de administração, estricnina (STR; 75 mg / kg) com i.p. via, pilocarpina (400 mg / kg) com s.c. rota e convulsão induzida por MES de eletrochoque máximo em modelos de camundongos. As atividades de estresse oxidativo, ou seja, superóxido dismutase (SOD), glutationa (GSH) e peroxidação lipídica (LPO), bem como ácido gama-aminobutírico (GABA) nos cérebros de camundongos convulsivos induzidos por PTZ. O tratamento com DVS aumentou a latência para desenvolver crises e diminuiu a mortalidade em roedores contra convulsões induzidas por PTZ, STR e pilocarpina. Os resultados de siezures conduzidos por MES revelaram que o DVS reduziu significativamente a duração e a mortalidade da extensão tônica dos membros posteriores. Os níveis de cérebro, SOD, GSH e GABA aumentaram significativamente (P < 0,01) e o LPO reduziu significativamente (P < 0,01) após o tratamento com DVS. Além disso, o DVS não apresentou sinais de coordenação motora no teste do rotarod. Demonstramos o papel do DVS na gênese da convulsão em camundongos sob condição de controle e atenua o dano oxidativo induzido por PTZ.


Subject(s)
Male , Animals , Mice , Anticonvulsants/administration & dosage , Seizures/drug therapy , Oxidative Stress/drug effects , Pentylenetetrazole/adverse effects , Desvenlafaxine Succinate/pharmacology , Depressive Disorder/drug therapy , Mice
2.
Braz. j. biol ; 832023.
Article in English | LILACS-Express | LILACS, VETINDEX | ID: biblio-1469094

ABSTRACT

Abstract Desvenlafaxine succinate (DVS) inhibits serotonin reuptake selectively and is approved for major depressive disorders. This research investigated influence of DVS on modulating brain monoamine and oxidative stress in mice. The antiepileptic potential of DVS (10, 20, or 30 mg/kg/i.p.) in pentylenetetrazole (PTZ; 85 mg/kg) with i.p. route of administration, strychnine (STR; 75 mg/kg) with i.p. route, pilocarpine (400 mg/kg) with s.c. route and maximal electroshock MES-induced convulsion in mouse models. The activities of oxidative stress, i.e. superoxide dismutase (SOD), glutathione (GSH) and lipid peroxidation (LPO) as well as gamma-aminobutyric acid (GABA) in the brains of PTZ-induced convulsive mice. Treatment with DVS increased the latency to develop siezures and declined mortalities in rodents against PTZ, STR and pilocarpine-induced convulsions. Results of MES-leaded siezures revealed that DVS reduced tonic hind limb extension duration and mortalities significantly. Brain, SOD, GSH and GABA level were significantly (P 0.01) increased and LPO reduced significantly (P 0.01) after DVS treatment. Furthermore, the DVS did not show any motor coordination signs in the rotarod test. We demonstrated that the role of DVS in convulsion genesis in mice under control condition and attenuate the PTZ-induced oxidative damage.


Resumo O succinato de desvenlafaxina (DVS) inibe seletivamente a recaptação da serotonina e é aprovado para transtornos depressivos maiores. Esta pesquisa investigou a influência do DVS na modulação da monoamina cerebral e do estresse oxidativo em camundongos. O potencial antiepiléptico de DVS (10, 20 ou 30 mg / kg / i.p.) Em pentilenotetrazole (PTZ; 85 mg / kg) com i.p. via de administração, estricnina (STR; 75 mg / kg) com i.p. via, pilocarpina (400 mg / kg) com s.c. rota e convulsão induzida por MES de eletrochoque máximo em modelos de camundongos. As atividades de estresse oxidativo, ou seja, superóxido dismutase (SOD), glutationa (GSH) e peroxidação lipídica (LPO), bem como ácido gama-aminobutírico (GABA) nos cérebros de camundongos convulsivos induzidos por PTZ. O tratamento com DVS aumentou a latência para desenvolver crises e diminuiu a mortalidade em roedores contra convulsões induzidas por PTZ, STR e pilocarpina. Os resultados de siezures conduzidos por MES revelaram que o DVS reduziu significativamente a duração e a mortalidade da extensão tônica dos membros posteriores. Os níveis de cérebro, SOD, GSH e GABA aumentaram significativamente (P 0,01) e o LPO reduziu significativamente (P 0,01) após o tratamento com DVS. Além disso, o DVS não apresentou sinais de coordenação motora no teste do rotarod. Demonstramos o papel do DVS na gênese da convulsão em camundongos sob condição de controle e atenua o dano oxidativo induzido por PTZ.

3.
Article in Chinese | WPRIM | ID: wpr-906489

ABSTRACT

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.

4.
Article in Chinese | WPRIM | ID: wpr-906433

ABSTRACT

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<sup>-1</sup>) and Chloriti Lapis group (2 g·kg<sup>-1</sup>). 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<sup>+</sup>, K<sup>+</sup>, Ca<sup>2+</sup> 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.

5.
Article | IMSEAR | ID: sea-200512

ABSTRACT

Background: Presently available antiepileptic drugs are effective in controlling seizures in more than half of patients of all epilepsy but use is often limited by adverse effects. H1 receptor antagonists, have a controversial status in patients of epilepsy. Both pro and antiepileptic effect has been documented in various animal studies. Hence, this study was designed to see the effect of promethazine, an H1 antihistaminic drug and its interactions with antiepileptic drugs lorazepam and sodium valproate in rats.Methods: The effect of promethazine (10 mg/kg) and its interactions with antiepileptic drugs lorazepam and sodium valproate was assessed by using maximal electroshock seizures (MES) and chemoshock pentylenetetrazol (PTZ) method.Results: Promethazine along with lorazepam and sodium valproate in subtherapeutic doses exerted significant protection against MES induced seizures whereas no such protection was observed with PTZ method rather the seizure threshold was reduced.Conclusions: Subtherapeutic doses of promethazine alone and in combination with lorazepam and sodium valproate showed protection against seizures in MES method. However, proconvulsant effect was seen with PTZ method. This shows dual behavior of promethazine on MES and PTZ induced seizures.

6.
Int. j. morphol ; 37(1): 265-272, 2019. graf
Article in English | LILACS | ID: biblio-990037

ABSTRACT

SUMMARY: Currently many people with epilepsy do not have seizure control even with the best available medications. Moreover various antiepileptics have adverse cognitive impact with other side effect. Thus, need for new antiepileptic drugs still remains challenge. However, many of the natural components have antiepileptic action and this fact remains scientifically unexplored. This study was designed to check the behavioral and neuro-pathological outcome of 1-Triacontanol cerotate (1TAC), isolated from Marsilea quadrifolia Linn. (MQ) on chronic Pentylenetetrazol (PTZ) kindling model of epilepsy in rats. Two-month-old adult male Wistar rats (n=60) were randomly divided into six groups; Group I (Cage Control), II (Vehicle Control), III (Positive Control), IV (Standard drug treated), V (1TAC: 40 mg/kg) & VI (1TAC: 80 mg/kg). To induce kindling a 35 mg/kg dose of PTZ was injected i.p. in every 48 hrs for 30 days in Group III to VI. Spatial memory performance was tested using Morris water maze, following which brains were further processed for histopathological investigations. Interestingly, 1TAC was able to minimize the loss of pyramidal cells in hippocampal CA3 region. These cellular changes were behaviorally responded as improved special learning and memory, a better spatial navigation and object place configuration. The current study strongly implicates that 1TAC from MQ has potent neuroprotective role and augments special memory deficit in chronic epileptic rats. The isolated component which attenuates spatial memory performance could be beneficial outcome to retain cognitive blunting in chronic epilepsy.


RESUMEN: Actualmente, muchas personas con epilepsia no cuentan con un control adecuado de las convulsiones, incluso con los mejores medicamentos disponibles. Además, varios antiepilépticos tienen un impacto cognitivo adverso además de efectos secundarios. Por lo tanto, la necesidad de nuevos fármacos antiepilépticos sigue siendo un desafío. Sin embargo, muchos de los componentes naturales tienen acción antiepiléptica y este hecho permanece científicamente inexplorado. Este estudio se diseñó para verificar el resultado conductual y neuro-patológico del cerotato de 1-triacontanol (1TAC), aislado de Marsilea quadrifolia Linn. (MQ) en el modelo de epilepsia en ratas del pentilenetetrazol (PTZ) crónico (PTZ). Ratas Wistar adultas de dos meses de edad (n = 60) se dividieron aleatoriamente en seis grupos; Grupo I (Control de jaula), II (Control de vehículo), III (Control positivo), IV (Medicamento estándar de tratamiento), V (1TAC: 40 mg / kg) y VI (1TAC: 80 mg / kg). Para inducir la inflamación se inyectó una dosis de 35 mg / kg de PTZ i.p. en cada 48 horas durante 30 días en los grupos III a VI. El rendimiento de la memoria espacial se probó utilizando el laberinto de agua de Morris, después de lo cual se procesaron los cerebros para investigaciones histopatológicas. Curiosamente, 1TAC pudo minimizar la pérdida de células piramidales en la región CA3 del hipocampo. Estos cambios celulares respondieron de manera conductual como una mejora del aprendizaje especial y la memoria, una mejor navegación espacial y la configuración del lugar del objeto. El estudio actual implica fuertemente que 1TAC de MQ tiene un potente papel neuroprotector y mejora el déficit de memoria especial en ratas epilépticas crónicas. El componente aislado que atenúa el rendimiento de la memoria espacial podría ser un resultado beneficioso para retener la reducción cognitiva en la epilepsia crónica.


Subject(s)
Animals , Male , Rats , Marsileaceae/chemistry , Epilepsy/drug therapy , Fatty Alcohols/administration & dosage , CA3 Region, Hippocampal/drug effects , Spatial Memory/drug effects , Pentylenetetrazole/adverse effects , Chronic Disease , Rats, Wistar , Pyramidal Cells , Epilepsy/chemically induced , Fatty Acids , Fatty Alcohols/isolation & purification , Morris Water Maze Test , Hippocampus/drug effects
7.
Article | IMSEAR | ID: sea-199738

ABSTRACT

Background: Current antiepileptic drugs (AEDs) are effective in controlling seizures in about 70% patients but use is often limited by adverse effects. Promethazine, H1 receptor antagonist, has a controversial status in patients of epilepsy. Both pro and antiepileptic effect has been documented in various animal studies. Hence, this study was designed to see the effect of promethazine, an H1 antihistaminic drug and its interactions with antiepileptic drugs in rats.Methods: The effect of promethazine (10mg/kg) and its interactions with antiepileptic drugs diazepam and phenytoin was assessed by using maximal electroshock seizures (MES) and chemoshock (PTZ) method.Results: Promethazine along with diazepam in subtherapeutic doses exerted significant protection against MES induced seizures whereas no such protection was observed with PTZ method rather the seizure threshold was reduced.Conclusions: Subtherapeutic doses of Promethazine alone and in combination with diazepam showed protection against seizures in MES method. However, proconvulsant effect was seen with PTZ method suggesting histamine plays a protective role in development of seizures. This shows dual behavior of promethazine on MES and PTZ induced seizures.

8.
Article in Chinese | WPRIM | ID: wpr-950423

ABSTRACT

Objective: To evaluate the protective effect of morin against pentylenetetrazol (PTZ)-induced tonic-clonic convulsions in mice. Methods: Swiss albino mice (18-22 g) was used to induce convulsions by intraperitoneal (i.p.) administration of PTZ (90 mg/kg). Mice were either pretreated with morin (10, 20 and 40 mg/kg) or vehicle (distilled water, 10 mg/kg) 45 min before PTZ administration. Various behavioral and biochemical parameters were assessed. Results: PTZ administration resulted in significant production (P<0.001) of tonic-clonic conclusion and mortality in mice. PTZ-induced increase in the duration of convulsion, onset of convulsion and mortality was inhibited significantly by morin (20 and 40 mg/kg) administration. The PTZ-induced decrease in brain GABA, dopamine and Na

9.
Article in Chinese | WPRIM | ID: wpr-700137

ABSTRACT

Objective: To evaluate the protective effect of morin against pentylenetetrazol (PTZ)-induced tonic-clonic convulsions in mice. Methods: Swiss albino mice (18-22 g) was used to induce convulsions by intraperitoneal (i.p.) administration of PTZ (90 mg/kg). Mice were either pretreated with morin (10, 20 and 40 mg/kg) or vehicle (distilled water, 10 mg/kg) 45 min before PTZ administration. Various behavioral and biochemical parameters were assessed. Results: PTZ administration resulted in significant production (P<0.001) of tonic-clonic conclusion and mortality in mice. PTZ-induced increase in the duration of convulsion, onset of convulsion and mortality was inhibited significantly by morin (20 and 40 mg/kg) administration. The PTZ-induced decrease in brain GABA, dopamine and Na+K+ATPase levels and increase in xanthine oxidase activity were inhibited significantly by morin (20 and 40 mg/kg) treatment. The increased levels of malondialdehyde and nitric oxide level were significantly decreased by morin (20 and 40 mg/kg) treatment. Also, reduced levels of superoxide dismutase and glutathione were increased significantly by morin treatment. Conclusions: Results of the present study indicate that morin showed its anti-convulsant effect via modulating the levels of brain GABA, Na+K+ATPase, and oxido-nitrosative stress. Thus, morin can be a potential candidate for further clinical evaluations as an anti-epileptic agent.

10.
Article in English | WPRIM | ID: wpr-975469

ABSTRACT

INTRODUCTION:Alcohol (EtOH) use disorders (AUDs) represent a substantial public health problem worldwide. Over 76million people present with AUDs 2.5 million deaths were attributed to alcohol (World Health Organization,2010). Channadshelshi has been used for treatment of alcohol-related, liver disease and intoxication intraditional medicine.GOAL:To determine effect of channadshelshi on voluntary alcoholic wistar rats.MATERIALS AND METHODS:To examine acute toxicity of Channadselshi were used V.P.Prozorovsky express method (1978) andOECD (2001).Voluntary EtoH consumption measurement (two-bottle choice, intermittent access to EtOH paradigm inwistar rats). Water and 20% ethanol were presented in 200 mlgraduated plastic cylinders with stainlesssteeldrinking spouts.The experiment period was 10 weeks total. EtOH consumption was expressed asgrams of EtOH consumed per kilogram of body weight/day.Elevated plus maze. Anxiety associated with EtoH withdrawalwas measured on EPM The mazewaselevated 1 m above the floor and contained four 50 cm long, 10 cmwidearms arranged at rightangles. The closed arms had opaque walls 30cm high, extending the length of the arm. At the time of thetest, eachanimal was placed in the center of the maze facing an open arm andallowed to explore for a5 min session. During this 5 min test session, theanimal’s number of arm entries and time spent in eacharm per entry was recorded on a camera.Pentylenetetrazol (PTZ) 100 mg/kg dose used in this study was determined as the dose that inducedseizures and protection against mortality in miceThe experimental protocol was approved by the Ethics Committee of the MNUMS. (№ 14-11/1À)RESULTS:LD50 of Channadselshi extract was found to be LD50=2.58 (2.1-3.2) gr/kg by V.P.Prozorovsky expressmethod (1978). Channadselshi was no acute toxic by OECD (2001).Ten and four weeks oral administration of Channadselshi (200 mg/kg) significantly (P<0.01) decreasedthe consumption of ethanol and significantly (P<0.01) increased time spent in open arm (EPM) involuntary alcoholic wistar rat compare to control.The time (sec) of latency the generalized convulsion were significantly (P<0.01) increased ofChannadselshi compare to control. The percent of protection against mortality were 80% in PTZinduced seizure in mice.CONCLUSIONS:1. Our study showed that Channadselshi hasreduced consumption of ethanol in voluntary alcoholicwistar rat.2. Channadselshi has central nervous system protection effect against PTZ induced seizure in mice.

11.
Journal of Clinical Pediatrics ; (12): 1176-1180, 2014.
Article in Chinese | WPRIM | ID: wpr-457917

ABSTRACT

Objective To explore the effects of mouse nerve growth factor (mNGF) on expression of metallothionein I/II (MT I/II) and cytochrome C (Cyt C) in hippocampus of pentylenetetrazol (PTZ)-induced epileptic (EP) young rats. Methods Fif-ty SD rats aged 19 days were randomly divided into control group, EP group, mNGF low, medium, and high dose groups. Each group had 10 rats. Control group was injected with normal saline every day, and EP group was intraperitoneally injected with PTZ 40 mg/(kg·d) for 21 days in succession. The mNGF low, medium, and high dose groups were respectively intramuscularly injected with mNGF 500, 1 000, 2 000 AU/(kg·d) for 7 days in succession after PTZ injection. Changes of body weight, behav-ioral performance were recorded. The positive cells of MT I/II, Cyt C were examined by immunohistochemisty. The levels of MT I, Cyt C mRNA in hippocampus were measured by real-time PCR. Results The number of MT I/II, Cyt C positive cells and the levels of MT I, Cyt C mRNA in hippocampus had signiifcant differences among groups (F=15.98-105.76, P=0.000). The number of MT I/II, Cyt C positive cells and the levels of MT I, Cyt C mRNA of EP group were higher than those in control group, mNGF low, medium, and high dose groups (P0.05). Conclusions As a stress protein, metallothionein is involved in the process of chronic epilepsy along with Cyt C. mNGF has neuroprotective effects on the hippocampus of epileptic rats in dose dependent manner.

12.
The Journal of Practical Medicine ; (24): 3735-3738, 2014.
Article in Chinese | WPRIM | ID: wpr-461667

ABSTRACT

Objective To investigate the dynamic expression of the drug resistance protein P-glycoprotein (P-gp) within 72 hours in the pentylenetetrazol (PTZ)-induced status epilepticus (SE) model, and to identify the optimal detection time to inhibit P-gp. Methods mRNA and protein expressions of P-gp in rats hippocampal tissue were detected by using immunohistochemistry , RT-qPCR and Western blot at different time points after modeling (0, 3, 6, 12, 24, 48, 72 h). Results The mean density of P-gp protein in the hippocampus of status epilepticus model was 0.325 1 ± 0.008 2 at 24 h, and was 0.396 3 ± 0.016 8 at 48 h, which were consistently higher than those of the control group (P < 0.05, P < 0.01, respectively). Results of qRT-PCR showed that MDR1a expression was significantly upregulated at 24 h and at 48 h (P < 0.05, P < 0.01, respectively). Western blot assay revealed that P-gp protein was also significantly increased at 48 h after seizures (P < 0.05). Conclusions The upregulation of P-gp after SE peaked at 48 h, which maybe the optimal detection time to detect drug resistant after SE.

13.
Article in Chinese | WPRIM | ID: wpr-451178

ABSTRACT

This study was aimed to observe the effect of Compound Shi-Chang-Pu (CSCP) granula on behavior, structure changes of hippocampus with epileptic seizure of mice induced by pentyenetetrazole (PTZ). Sixty Kunming mice, which were half male and half female, were randomly divided into 6 groups, which were the blank control group, animal model, phenytoin (PHT) group, high-dose CSCP (4 000 mg·kg-1) group, middle-dose CSCP (2 000 mg·kg-1) group and low-dose CSCP (1 000 mg·kg-1) groups. The blank group and model group were given intragas-tric administration the same volume of saline, the others animals treated with continuous oral administration of drugs for 7 days. Intraperitoneal injection of PTZ (80 mg·kg-1) was given 1 h after the last medication to establish the a-cute epilepsy model (expect the blank control group). Observation was made on the influence of CSCP on incubation period, behavior degree and times of epileptic seizure among PTZ induced epilepsy mice, the structure changes of mice were detected by the brain tissue HE staining. The results showed that CSCP can improve the degree of seizure attack, prolong the incubation period of mild attack, and decrease Ⅳ and Ⅴ degree epileptic seizure, the PTZ in-duced epilepsy mice could damage the structure of hippocampus, reduce the number of cells, PHT and CSCP could ameliorate these changes. It was concluded that CSCP had certain inhibition on epileptic seizure mice induce by PTZ and ameliorate the damage of hippocampus. The antiepileptic mechanism still requires futher study.

14.
Article in English | IMSEAR | ID: sea-153942

ABSTRACT

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.

15.
Article in Chinese | WPRIM | ID: wpr-436036

ABSTRACT

Objective To detect the expression of extracellular-regulated kinase (ERK) and phosphatedextracellular-regulated kinase (P-ERK) in the hippocampus after pentylenetetrazoloe-induced status epilepsy and the effects of nimodipine on it.Methods Male Sprague-Dawley adult rats (200-250 g) were randomly divided into normal control group(NC,n =35),status epilepsy group (SE,n =40),nimodipine group (NIM,n =40).The rats were injected first with 40 mg/kg pentylenetetrazoloe(PTZ),followed 10 minutes later by 20 mg/kg PTZ,and subsequently,10 mg/kg PTZ ip every 10 minutes until SE occurred,apoint charactered by a loss of postural control and tonic-clonic seizures.Rats in control group received the same number of saline injections.Rats in NIM group were injected NIM(2.5 mg/kg) intraperitoneally 15 min before the injection of PTZ.Rats in every group were killed at 30 minutes,1 hour,3 hours,12 hours,24 horus,72 hours and 7 days after status epilepsy respectively and the hippocampus were dissected.The expression of ERK and P-ERK in the hippocampus were detected by Western blot.Results Nimodipine attenuated the convulsion of PTZ-induced status epilepsy.There was dynamic expression of P-ERK in SE group.In NIM group,the expression of P-ERK was markedly increased than that of SE group at 30 min,1h,3h,12h,24h,72h,and 7d (3.26 ±0.95 vs 2.56 ±0.82 at 30 min,P<0.05).Conclusion Nimodipine attenuates the convulsion of PTZ-induced status epilepsy with increased expression of phosphated-ERK in the hippocampus of rats.

16.
Rev. bras. farmacogn ; 22(3): 323-329, May-June 2012. graf, tab
Article in English | LILACS | ID: lil-624684

ABSTRACT

The aim of the present study was to evaluate the anticonvulsant effects of alcoholic root extract of Cardiospermum halicacabum L., Sapindaceae (ARECH), on the various murine models of epilepsy. The root extract of the plant was administered p.o. to male swiss albino mice at doses of 30, 100 and 300 mg/kg before evaluation. The brain monoamine levels were determined after two days administration. ARECH at doses of 100 and 300 mg/kg significantly delayed the onset of clonus and tonus in pentylenetetrazol, isoniazid and picrotoxin-induced convulsions. Tonic hind limb extension was also decreased at doses of 100 and 300 mg/kg as compared to vehicle control in maximal electroshock model. No significant motor toxicity was observed even at a highest dose administered, i.e. 900 mg/kg. Brain monoamine analysis by HPLC revealed a significant increase in GABAergic activity in C+ (in cerebellum) and C- (except cerebellum). These results suggested that ARECH possesses a significant anticonvulsant activity with a low motor toxicity profile. This activity may be attributed to an increase in GABAergic activity.

17.
Article in Chinese | WPRIM | ID: wpr-964563

ABSTRACT

@#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.

18.
Colomb. med ; 39(3,supl): 46-50, jul.-sept. 2008. tab
Article in Spanish | LILACS | ID: lil-573400

ABSTRACT

Objetivo: El incremento en el contenido de GABA cerebral o la administración de un agente GABA-mimético se emplea como un tratamiento antiepiléptico eficaz. Sin embargo, se sugiere que el empleo de farmacos que alteran continuamente la transmisión sinoptica puede afectar al sistema nervioso. En el presente estudio se evaluaron los efectos del pretratamiento agudo (una administración) y subcrónico (administraciones diarias por 7 días) de diazepam (DZP; 10 mg/kg, ip), gabapentina (GBP, 100 mg/kg, vo) y vigabatrina (VGB, 500 mg/kg, vo) en las crisis generalizadas inducidas por pentilenetetrazol (PTZ, 80 mg/kg ip). Materiales y métodos: Ratones macho de la cepa taconic (20-25 g) recibieron tratamiento agudo y subcrónico de DZP, GBP o VGB y 24 h después de la última administración se aplicó PTZ. Se evaluaron las latencias a la primera crisis clónica, a la fase tónica así como la incidencia de muerte. Resultados: El pretratamiento agudo con DZP protegió 100 por ciento a los animales de los efectos del PTZ, mientras que su administración subcrónica redujo la latencia a la crisis clónica (21 por ciento; p<0.05), la fase tónica (27 por ciento, p<0.05) y muerte (37 por ciento, p<0.05). La aplicación aguda de VGB protegió 100 por ciento a los animales de los efectos del PTZ, mientras que su aplicación subcrónica aumentó la latencia a las crisis clónicas (32 por ciento, p<0.05), aunque facilitó la aparición de la crisis tónica (55 por ciento, p<0.05) y la muerte (58 por ciento, p<0.05). La administración aguda de GBP elevó la latencia a la crisis clónica (52 por ciento, p<0.05), mientras que su administración subcrónica no modificó el efecto producido por PTZ. Conclusiones: Estos resultados sugieren que el pretratamiento agudo y subcrónico de farmacos que incrementan la transmisión GABAérgica modifican diferencialmente la susceptibilidad a las crisis por PTZ y que su administración repetida puede facilitar la producción de crisis convulsivas.


Objetives: The increased GABA content or administration of a centrally active GABA-mimetic agent have been used as a efficacious anticonvulsant therapeutic approach. However, it has been suggested that the use of drugs that continually and noncontingently alter synaptic transmission could alter at the nervous system. The present study was carried out to investigate the effects of acute (one administration) and subchronic (7 daily administrations) treatments with Diazepam (DZP; 10 mg/kg, ip), Gabapentin (GBP, 100 mg/kg. vo) and Vigabatrin (VGB, 500 mg/kg, vo) on pentylenetetrazol-induced generalized seizures (PTZ, 80 mg/kg, ip). Materials and methods: Male Taconic mice (20-25 g) received acute or subchronic treatment with DZP, VGB or GBP and 24 h after the last administration, the effects of PTZ (latency to the clonus, forelimb extension and death incidence) were evaluated. Results: Acute DZP protected all animals (100 percent) to the convulsant effects of PTZ, whereas subchronic DZP decreased the latency to the clonic (21 percent; p<0.05), tonic (27 percent, p<0.05) and death (37 percent, p<0.05). The acute treatment with VGB protect all animals (100 percent) to the effects of PTZ, whereas its subcronic administration enhanced the latency to clonus (32 percent, p<0.05), but facilitated the appearance of tonic seizures (55 percent, p<0.05) and death (58 percent, p<0.05). The acute administration of GPB increased the latency to clonus (52 percent, p<0.05), whereas its subchronic treatment did not modify the PTZ-induced effects. Conclusions: The present results indicate that the acute pretreatment with drugs enhancing GABAergic transmission differently modifies the seizure susceptibility, and that the subchronic administration may facilitate the seizure activity.


Subject(s)
Mice , Diazepam , Epilepsy , Mice , Nervous System
19.
Article in Chinese | WPRIM | ID: wpr-680117

ABSTRACT

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

20.
Article in Chinese | WPRIM | ID: wpr-563816

ABSTRACT

Objective:To study e ects of Saikosaponin a(SSa) on tumour necrosis factor-alpha(TNF-?) release and its receptor expression in cultured hippocampal astrocytes induced by pentylenetetrazol(PTZ).Methods:The in vitro cultured primary hippocampal astrocytes were randomly divided into control group(group A),PTZ-induced group(group B)PTZ10mmol/L+SSa groups(group C and group D,the SSa concentrations were 1.25mg/L and 0.625mg/L respectively).The extracellular uid TNF-? level and the expression of tumour necrosis factor receptor type 1(TNFR1) in hippocampal astrocytes were respectively detected by ELISA and Western-blot after PTZ-induced 2 hours.Results:the TNF-? level and TNFR1 expression of group B were signi cantly higher than that of group A,group C and group D(P

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