Differential Hippocampal Protection when Blocking Intracellular Sodium and Calcium Entry during Traumatic Brain Injury in Rats

摘要

This study investigated the contributions of the reverse mode of the sodium-calcium exchanger (NCX) and thentype 1 sodium-proton antiporter (NHE-1) to acute astrocyte and neuronal pathology in the hippocampus followingnfluid percussion traumatic brain injury (TBI) in the rat. KB-R7943, EIPA, or amiloride, which respectivelyninhibit NCX, NHE-1, or NCX, NHE-1, and ASIC1a (acid-sensing ion channel type 1a), was infused intraventricularlynover a 60-min period immediately prior to TBI. Astrocytes were immunostained for glialnfibrillary acidic protein (GFAP), and degenerating neurons were identified by Fluoro-Jade staining at 24 h afterninjury. Stereological analysis of the CA2/3 sub-regions of the hippocampus demonstrated that higher dosesnof KB-R7943 (2 and 20 nmoles) significantly reduced astrocyte GFAP immunoreactivity compared to vehicletreatednanimals. EIPA (2–200 nmoles) did not alter astrocyte GFAP immunoreactivity. Amiloride (100 nmoles)nsignificantly attenuated the TBI-induced acute reduction in astrocyte GFAP immunoreactivity. Of the threencompounds examined, only amiloride (100 nmoles) reduced hippocampal neuronal degeneration assessed withnFluoro-Jade. The results provide additional evidence of acute astrocyte pathology in the hippocampus followingnTBI, while suggesting that activation of NHE-1 and the reverse mode of NCX contribute to both astrocytenand neuronal pathology following experimental TBI.