PROTECTIVE EFFECT OF ANTI-EPILEPTIC AGENT Q808 ON NEURONAL DAMAGE IN A RAT MODEL OF TEMPORAL LOBE EPILEPSY

Abstract

The detailed effect of Q808 (6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine) which has been demonstrated to have anti-epileptic activity, on the protection from neuronal damage in temporal lobe epilepsy (TLE) still remains unclear. The purpose of this study was to evaluate the protective effects of Q808 on neuronal damage by exploring its mechanism of hippocampal neuronal apoptosis in a rat model of TLE. Fifty rats were divided equally into five groups. The normal group [Formula: see text] served as the normal non-seizure and untreated group. To induce the TLE model, pilocarpine (20[Formula: see text]mg/kg) was intraperitoneally administered to the other 40 rats; 33 rats successfully developed TLE status. Subsequently, the TLE group [Formula: see text], VPA group [Formula: see text], Q808-L group [Formula: see text], and Q808-H group [Formula: see text] were, respectively, treated with 5[Formula: see text]ml normal saline, 1[Formula: see text]ml/kg valproate, 0.5[Formula: see text]ml/kg Q808, and 1[Formula: see text]ml/kg Q808 solution once daily for 28 days. The Morris water maze test was performed to evaluate the effects of Q808 on cognitive impairment in the TLE model. Hematoxylin-eosin (HE) staining was performed to determine histopathological changes in the hippocampus, immunohistochemistry was performed to determine the expression of caspase-3 in the hippocampus, and western blotting was performed to determine the expression levels of apoptosis-related proteins, including Apaf-1, caspase-9, and caspase-3. Q808 decreased the expression levels of the apoptosis-related proteins in the TLE hippocampal tissue, and higher doses are more effective. Besides, Q808 did not impair spatial cognition and memory. Furthermore, the results indicated that Q808 treatment inhibited neuronal cell death, and significantly decreased the expression levels of apoptotic factors, including Apaf-1, caspase-9, and caspase-3. Q808 prevented neuronal damage in the hippocampus of TLE rats by targeting the intrinsic apoptotic pathway of neurons.