Abstract

Overexpression of Synaptic Vesicle Protein 2A Inhibits Seizures and Amygdaloid Electroencephalogram Activity in Pilocarpine-induced Pharmacoresistant Epileptic Rats

Author(s): Likun Wang, Xin Zhou, Jing Shi, Guofeng Wu, Zhen Hong

Abstract

Purpose: The present study invest igated the role of upregulation of synaptic vesicle protei n2A (SV2A) in seizure control and electroencephalogram (EEG) activity in pilocarpine-inducedpharmacoresistant epileptic rats.

Methods: A total of 100 healthy adult male Sprague-Dawley rats were used to establish t  hep il ocarpine-induced model of epilepsy. The successful epilepsy model was then used to selectfor pharmacoresistance by testing seizure responses to phenobarbital and carbamazepine.The selected pharmacoresistant rats were assigned to a pharmacoresistant epileptic group(PRE group, 10 rats) or a SV2A upregulation group (PRU group, 8 rats). Ten pharmacosensitive
epileptic rats (PSE group, 10 rats) selected randomly and 10 norma l rats (NCR group,  10  rats)served as controls. Immunohistochemistry and western blots were performed to assess SV2Aexpression in hippocampal tissue samples from all 4 groups. EEG changes and epilepticseizures were recorded by video-EEG and compared among the groups.

Results: Immunohistochemical staining  showed that SV2A levels increased slightly in the   P S   Egroup (0.26 ± 0.018) compared with the NCR group (0.24 ± 0.031). However, SV2A decreasedremarkably in the PRE group (0.11 ± 0.121). Western blot analysis yielded similar findings.SV2A increased in the PSE group (4.10 ± 1.127) compared with the NCR group (3.26 ± 0.699)and decreased in the PRE group (1.86 ± 0.421). Frequency and duration of seizures increasedin the PRE group as compared with the PSE group. After overexpression of SV2A, levels of SV2Aprotein increased in the PRU group. In addition, seizure severity, frequency, and duration weredecreased compared with the PRE group.

Conclusion: SV2A might be associate d with epileptogenesis of pharmacoresistance inpilocarpine-induced epileptic rats.


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