Mechanisms Of Central Noradrenergic Neurons In The Regulation Of Sudden Death In Epilepsy (SUDEP)

Objective:Using the DBA / 1 mouse model of sudden unexpected death in epilepsy(SUDEP)to study the mechanism of norepinephrine α-1 receptor(NEα-1R)in the regulation of seizure-induced respiratory arrest(S-IRA).Methods: The DBA/1 mouse SUDEP model was established by acoustic stimulation or intraperitoneal injection of PTZ to DBA/1mice,respectively.The mice from each model group were randomly divided into blank control group,atomoxetine / prazosin control group and prazosin experimental group.To compare whether there were significant differences in the incidence of S-IRA,seizure score,latency,duration of tonic-clonic seizures,heart rate,blood pressure,EEG,and brain stem TH content among the groups were accepted.Results:In our model,the lower incidence of S-IRA by atomoxetine can be significantly reversed by intraperitoneal or intracerebroventricular injection of prazosin,a selective antagonist of NEα-1R.No obvious difference was observed in the EEG data of the cerebral cortex between the atomoxetine control group and the prazosin experimental group in the PTZ injection SUDEP model.In addition,repeated acoustic stimulation or S-IRA was associated with the decreased activity of TH,but did not lead to a decrease in the content of TH in the brainstem of DBA / 1mice.Conclusion: Our data suggested that deficiency of norepinephrine transmission contributed to seizure-induced respiratory arrest and NEα-1R in the brain may be a potential and specific target to prevent SUDEP.