APOEε4 increases trauma induced early apoptosis via reducing delayed rectifier K+ currents in neuronal/glial co-cultures model.

Traumatic brain injury (TBI) is a commonly encountered emergency and severe neurosurgical injury. Previous studies have shown that the presence of the apolipoprotein E ( APOE ) ε4 allele has adverse outcomes across the spectrum of TBI severity. Our objective was to evaluate the effects of APOE alleles on trauma induced early apoptosis via modification of delayed rectifier K + current ( I k(DR) ) in neuronal/glial co-cultures model. An ex vivo neuronal/glial co-cultures model carrying individual APOE alleles ( ε2, ε3, ε4 ) of mechanical injury was developed. Flow cytometry and patch clamp recording were performed to analyze the correlations among APOE genotypes, early apoptosis and I k(DR) . We found that APOEε4 increased early apoptosis at 24 h ( p <0.05) compared to the ones transfected with APOEε3 and APOEε2 . Noticeably, APOEε4 significantly reduced the amplitude of the I k(DR) at 24 h compared to the APOEε3 and APOEε2 ( p <0.05) which exacerbate Ca 2+ influx. This indicates a possible effect of APOEε4 on early apoptosis via inhibiting I k(DR) following injury which may adversely affect the outcome of TBI. [ABSTRACT FROM AUTHOR]