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1.
Chinese Journal of Contemporary Pediatrics ; (12): 65-69, 2008.
Article in Chinese | WPRIM | ID: wpr-325632

ABSTRACT

<p><b>OBJECTIVE</b>To study the neuroprotective effects of topiramate (TPM) alone or together with folic acid (FA) on young rats with kindling-induced epilepsy.</p><p><b>METHODS</b>Rat models of epilepsy were prepared by pentylenetetrazol (PTZ)-induced kindling. Seventy-two 3-week-old male Wistar rats were randomly divided into 6 groups: four TPM-treated epilepsy groups (TPM 20, 40 or 80 mg/kg/d and TPM 40 mg/kg/d + FA 5 mg/kg/d), a positive control group (untreated epilepsy group) and a negative control group (normal control group). After two months of administration, behaviors of the rats were recorded; serum levels of neuron-specific enolase (NSE) were measured using ELISA; pathological changes in the hippocampus were observed.</p><p><b>RESULTS</b>The frequency of convulsion seizures in the 20, 40 and 80 mg TPM treatment and TPM+FA groups was 44.7 +/- 2.9, 44.3 +/- 3.1, 42.7 +/- 3.2, and 40.8 +/- 3.7 respectively, which were significantly lower than that in the positive control group (48.4 +/- 3.7) (P <0.01). Twenty, forty and eighty mg TPM treatment and TPM+FA treatment significantly reduced NSE levels from 35.71 +/- 5.97 microg/L of the control group to 27.40+/- 6.40, 24.79 +/- 6.22, 21.47 +/- 6.87 and 22.55 +/- 7.02 microg/L respectively (P <0.05). Neuronal apoptosis in the CA3 and CA1 regions were alleviated in the four TPM treatment groups compared with positive control. The number of necrotic neurons was progressively reduced with the increased dose of TPM. The 40 mg TPM+FA treatment group showed less necrotic neurons in the CA3 and CA1 regions than the 40 mg TPM alone treatment group.</p><p><b>CONCLUSIONS</b>TPM has protective effects against epilepsy-induced neuronal damage. The effect is dose-dependent. A combination of TPM and FA can produce a synergistic effect.</p>


Subject(s)
Animals , Male , Rats , Dose-Response Relationship, Drug , Enzyme-Linked Immunosorbent Assay , Epilepsy , Drug Therapy , Pathology , Folic Acid , Pharmacology , Fructose , Pharmacology , Hippocampus , Pathology , Kindling, Neurologic , Neuroprotective Agents , Pharmacology , Phosphopyruvate Hydratase , Blood , Rats, Wistar
2.
Journal of Applied Clinical Pediatrics ; (24)2006.
Article in Chinese | WPRIM | ID: wpr-639469

ABSTRACT

Objective To explore protective effect of topiramate (TPM) and folic acid (FA) on mitochondrial damage in hippocampal CA3 neurons during pentylenetetrazol- induced kindling in immature rats.Methods Pentylenetetrazol (PTZ) - induced kindling in rats was used to establish rat models of epilepsy.Forty-eight 3-week-old male Wistar rats were randomly divided into 4 groups: two therapy groups with TPM 40 mg/(kg?d) or TPM 40 mg/(kg?d) and FA 5 mg/(kg?d) administration, 2 control groups (positive control group and negative control group) with the equal amount of distilled water administration. The seizure behaviors of rats were evaluated. Two months later, the rats were killed and the brain sections were made. The mitochondrial ultrastructures of neurons in hippocampal CA3 region were observed with transmission electron microscope.Results In the positive control group, the frequency of seizure was (48.4 ? 3.7)times, while in TPM group (44.3 ? 3.1)times and in TPM and FA group(40.8 ? 3 .7)times.The differences were significant among three groups (Pa

3.
Journal of Applied Clinical Pediatrics ; (24)2006.
Article in Chinese | WPRIM | ID: wpr-639346

ABSTRACT

Objective To study the influence of valproate sodium(VPA)on neuroprotective effects of topiramate(TPM).Methods For-ty-eight 3-4 week-old male Wistar rats were randomly divided into 4 groups of 12 rats each.Group A was negative control rats,and groups B-D were rat model of epilepsy,induced by pentylenetetrazol(PTZ).The rats in 2 experimental groups were adminstered intragastrically with TPM 40 mg/kg and TPM 40 mg/kg+ VPA 200 mg/kg;2 control groups(groups A and B)with the equal amount of distilled water administration.After 2-month administration,changes of the behavior,levels of serum neuron-specific enolase(NSE)and the pathological in hippocampus were examined.Results The level of NSE in the group of TPM were significantly lower than that in masculine group,but no difference between masculine group and the TPM plus VPA.The pathological change in hippocampus were abatement in the group of TPM.Conclusion TPM plus high dosage of VPA will impaire the neuroprotective effects of TPM.

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