【Animal Modeling】-Preliminary study on the mechanism of hypoxic preconditioning reducing the susceptibility to epilepsy and its brain protective effect in rats

  Objective: To preliminarily investigate the effect of intermittent hypoxic preconditioning on epileptic seizures in rats induced by lithium chloride and pilocarpine and its brain protective mechanism.

  Methods: Ninety-six clean-grade SD rats were randomly divided into control group, epilepsy group and 4 intermittent hypoxic preconditioning + epilepsy groups. Epilepsy group and 4 intermittent hypoxic preconditioning + epilepsy groups (injected on 1, 3, 7, and 14 days after 5-day IHP preconditioning, respectively) were used to establish epilepsy models by intraperitoneal injection of lithium chloride-pilukapine. Then, 240 min seizure behavior, generalized seizure latency and percentage quantitative analysis were performed, and the cognitive function of rats was tested by water maze test. Then, the apoptosis of rat hippocampal neurons and related proteins (BCL-2, Bax and cleaved-caspase-3) were detected by TUNEL labeling and immunoblotting.

  RESULTS: Between 50 and 150 min after lithium chloride-pilukapine injection, the modified Racine score of epileptic seizures peaked. The average modified Racine score of the rats in the epilepsy group was significantly lower than that of the other groups 3 days after intermittent hypoxic preconditioning, and the generalized seizure latency and percentage of the group were also significantly different from those of the epilepsy group (P<0.05). Compared with the rats in the epilepsy group and the other three intermittent hypoxic preconditioning + epilepsy groups, the escape latency of the rats in the epilepsy group induced by intermittent hypoxic preconditioning 3 days later was shorter, and the number of neuronal apoptosis was lower. The percentage of dwell time in the target quadrant was higher (P<0.05). 3="" there="" were="" no="" significant="" differences="" in="" the="" water="" maze="" and="" apoptosis="" detection="" parameters="" between="" epilepsy-induced="" group="" control="" days="" after="" intermittent="" hypoxia="" preconditioning="" p="">0.05).

  Conclusion: IHP preconditioning reduces the susceptibility to epilepsy in rats by inhibiting abnormal apoptosis, and has a protective effect on the brain.