These observations are consistent with other in vivo studies indicating that astrocytes are vulnerable to both TBI and ischemia (Liu et al., 1999 Ouyang et al., 2007 Zhao et al., 2003). These immunocytochemical alterations are associated with morphological reduction in fine vellate process complexity with fewer processes and reduced astrocyte branching (Zhao et al., 2003). The reduction in GFAP immunoreactivity within hours after fluid percussion TBI is also associated with reduction in immunoreactivity for glutamine synthetase, another astrocyte-specific enzyme which catalyzes the formation of glutamine from glutamate. Previous experimental studies have shown disruption of key markers of astrocyte structure (e.g., glial fibrillary acidic protein ) and function (e.g., glutamine synthetase) in selectively vulnerable brain regions within 24 h after lateral fluid percussion TBI in rats (Zhao et al., 2003). R esearch on traumatic brain injury (TBI) and ischemia has typically focused on injury to neurons, although astrocyte damage has been documented to occur as a consequence of central nervous system (CNS) injury and is likely to contribute importantly to the pathophysiology of brain injury (Floyd and Lyeth, 2007). The results provide additional evidence of acute astrocyte pathology in the hippocampus following TBI, while suggesting that activation of NHE-1 and the reverse mode of NCX contribute to both astrocyte and neuronal pathology following experimental TBI. Of the three compounds examined, only amiloride (100 nmoles) reduced hippocampal neuronal degeneration assessed with Fluoro-Jade. Amiloride (100 nmoles) significantly attenuated the TBI-induced acute reduction in astrocyte GFAP immunoreactivity.

EIPA (2–200 nmoles) did not alter astrocyte GFAP immunoreactivity. Stereological analysis of the CA2/3 sub-regions of the hippocampus demonstrated that higher doses of KB-R7943 (2 and 20 nmoles) significantly reduced astrocyte GFAP immunoreactivity compared to vehicle-treated animals. Astrocytes were immunostained for glial fibrillary acidic protein (GFAP), and degenerating neurons were identified by Fluoro-Jade staining at 24 h after injury. KB-R7943, EIPA, or amiloride, which respectively inhibit NCX, NHE-1, or NCX, NHE-1, and ASIC1a (acid-sensing ion channel type 1a), was infused intraventricularly over a 60-min period immediately prior to TBI. This study investigated the contributions of the reverse mode of the sodium-calcium exchanger (NCX) and the type 1 sodium-proton antiporter (NHE-1) to acute astrocyte and neuronal pathology in the hippocampus following fluid percussion traumatic brain injury (TBI) in the rat.

Ncx 2000 xp serial numbers