[Protective effects of levetiracetam and simvastatin on pilocarpine-induced epilepsy in rat models].
OBJECTIVE
TO determine neuroprotective properties of levetiracetam and simvastatin using rats with pilocaroine-induced epilepsy.


METHODS
Epileptic rat models were randomly divided into 4 groups, each being exposed to saline, simvastatin, levetiracetam, or levetiracetam + simvastatin. Brain tissues of the rats were examined. Nissl staining was used to determine pilocarpine-induced neuronal loss in CA1 and CA3 of hippocampus. Western blot was used to detect calpain-1 expression of hippocampus.


RESULTS
Severe cell death was found 24 h after seizures, with a level significantly higher than the controls. Compared with the saline-treated cells, simvastatin did not decrease severe cell death (P>0.05), but levetiracetam and levetiracetam+simvastatin decreased severe cell death 24 h after seizures (P<0.05). No significant differences were found between those treated with levetiracetam and those with levetiracetam+simvastatin. Compared with controls, overexpressed calpain-1 was found in the rats 24 h after seizures, which indicates that calpain-1 may be involved in the pathophysiological mechanisms of epilepsy. Compared with those treated with pilocarpine + saline, simvastatin, levetiracetam and levetiracetam + simvastatin reduced the level of calpain-1 24 h after seizures (P<0.05).


CONCLUSIONS
Levetiracetam, not simvastatin, possesses neuroprotective properties, through changing calpain-1 expression levels. But levetiracetam plus simvastatin treatment does not have advantages over the choice of monotherapy. Simvastain does not possess neuroprotective properties at the early stage of epilepsy.
Meng-qiu
MQ
Li
Wen-wu
WW
Zhang
Tao
T
Chen
Ling
L
Liu
D000818:Animals; D002154:Calpain / Q000378:metabolism; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy*; D006624:Hippocampus / Q000473:pathology; D000077287:Levetiracetam; D010862:Pilocarpine / Q000009:adverse effects*; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D012640:Seizures / Q000503:physiopathology; D019821:Simvastatin / Q000494:pharmacology*
D010862:Pilocarpine; D000077287:Levetiracetam; D019821:Simvastatin; D002154:Calpain; D010889:Piracetam