[Neuroprotective effects of topiramate and folic acid on young rats with kindling-induced epilepsy].
OBJECTIVE
To study the neuroprotective effects of topiramate (TPM) alone or together with folic acid (FA) on young rats with kindling-induced epilepsy.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Wang
Ping
P
Department of Pediatrics, Fuzhou General Hospital of Nanjing Military Command, Fuzhou 350025, China. wangpingpan@126.com
Ren
Rong-Na
RN
Cai
Shu-Ying
SY
Chen
Xin-Min
XM
Ye
Li-Yan
LY
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D004827:Epilepsy / Q000188:drug therapy* / Q000473:pathology; D005492:Folic Acid / Q000494:pharmacology*; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000473:pathology; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010751:Phosphopyruvate Hydratase / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D000077236:Topiramate
D018696:Neuroprotective Agents; D000077236:Topiramate; D005632:Fructose; D005492:Folic Acid; D010751:Phosphopyruvate Hydratase