Dynamic Expression Of Fast Ripples In Rat Hippocampi After Status Epilepticus And The Potential Underlying Mechanisms

Objective:To assess the dynamic changes in the average and peak spectral power of fast ripples(FRs)in the hippocampi after interventions with valproate sodium(VPA),carbenoxolone(CBX),and quinine(QUIN).Methods:Sprague-Dawley rats were selected to establish a lithium–pilocarpine(pilo)epileptic model,and were assigned to a lithium–pilocarpine(PILO),VPA+PILO,QUIN+PILO,or CBX+PILO group.Intracranial electroencephalograph was recorded before and after status epilepticus(SE).Time-frequency analysis was used to analyze the dynamic changes in the FRs in the hippocampal CA1,CA3,and DG areas.The connexin(CX)43,CX32,and CX36 expressions in the rat hippocampal at different time-points were semi-quantitatively analyzed via western blotting.Results:Seizures induced CX43 expression,but had no significant effects on CX36 or CX32 expressions.Pretreatment with VPA,QUIN,and CBX had no significant effects on CX36 or CX32 expressions in normal rat hippocampus,but inhibited CX43,CX36,and CX32 expression after SE.Inhibition of CX32 expression with CBX was particularly obvious.The duration required for reaching stage IV seizure post-injection was greater in the intervention groups(VPA+PILO,QUIN+PILO,and CBX+PILO groups)than in the PILOgroup(p>0.05).The time required for the disappearance of SE after chloral hydrate injection was lower in the intervention groups(VPA+PILO,QUIN+PILO,and CBX+PILO groups)than that in the PILO group(p<0.05).The average spectral power of the FRs in the VPA+PILO and QUIN+PILO groups were significantly lower than that in the PILO group at 10 min after SE,10 min before chloral hydrate injection,and 10 min after chloral hydrate injection(p<0.05).The average spectral power of FRs in the CBX+PILO group was lower than that in the PILO group at10 min after SE(p<0.05).The average spectral power of FRs in the 3intervention groups recovered to the baseline level at 10 min after chloral hydrate injection and persisted for 3 days after SE.The dynamic changes were similar between average and peak spectral power of FRs.Conclusion:After SE,CX may participate in pathological FR generation by establishing abnormal electrical synaptic transmission,thus increasing the susceptibility to convulsion.The gap junctions(GJ)blockers can inhibit various CX expression,and thus decrease FR energy and alleviate the degree of seizure.Of note,the findings of the present study may contribute to development of new anti-epileptic drugs with novel mechanistic targets.