The Effects Of Chloroquine On Neuronal Autophagy In Hippocampus Of Rats With Status Epilepticus

OBJECTIVE:The present study aim to investigate the neuronal autophagy in rat hippocampus with pentamethazol-induced status epilepticus, and to probe the effects of chloroquine on neuronal autophagy, and explore the suppressing effects and mechanism of chloroquine in epilepsy process.METHODS:24 adult male Wistar rats were randomly divided into three groups, named control group, pentamethazol induced epilepsy group and chloroquine pretreatment group. The behavior and electroencephalogram of rats were observed and recorded within 2h after injection. The HE and Nissl staining were used to measure the degree of neuronal loss in cerebral cortex and CA1 area. And the levels of microtubule-associated protein light chain 3 (LC3) and P62 examined by immunohistochemical and Western blot were reflected to the expression of autophagy.RESULTS:No convulsion was emerged in the control group. Seizure intensity in the pentamethazol group was more severe than that in the chloroquine pretreatment group. Electroencephalogram recordings from hippocampus showed no epileptic spikes in the control group. There were high amplitudes with fast frequency signals in pentamethazol group, low-amplitude and slow frequency signals in chloroquine group. The HE and Nissl staining results showed that obvious neuronal loss was observed in both cortex and hippocampus CA1 area in pentamethazol group, the number of survival neuron cells was significantly reduced compared to control group (P<0.05). The level of LC3 and LC3 â…¡/LC3 â…  was significantly accumulated (P<0.05), and the level of p62 was notably lessened in comparison with the control group. According to the result of Nissl and Western blot, we can infer that chloroquine remarkably inhibited the process of autophagy and neuronal loss compared to pentamethazol group (P<0.05).CONCLUSION:Chloroquine partially inhibited the hyperactivation of autophagy in neuron cells, played a neuroprotective role in rats with status epilepticus induced by pentamethazol, and suppressed seizure to a certain extent, could be a potential antiepileptic drugs.