Akt/GSK3beta survival signaling is involved in acute brain injury after subarachnoid hemorrhage in rats.

Abstract

Apoptotic cell death is associated with acute brain injury after subarachnoid hemorrhage (SAH). The Akt/glycogen synthase kinase-3beta (GSK3beta) pathway plays an important role in the cell death/survival pathway after a variety of cell death stimuli. However, its role in acute brain injury after SAH remains unknown. We used an endovascular perforation model of SAH in rats. Phospho-Akt and phospho-GSK3beta expression was examined by Western blot analysis and immunohistochemistry. Terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL) and a cell death assay were used for detection of apoptosis. We administered LY294002 to examine the role of the Akt/GSK3beta pathway in the phosphoinositide 3-kinase pathway after SAH. Phosphorylation of Akt and GSK3beta was accelerated after SAH. In the cerebral cortex, where acute brain injury was the most severe, phosphorylation of these proteins was observed in the early phase after SAH. Cortical neurons with continuous Akt phosphorylation did not colocalize with TUNEL-positive cells at 24 hours. LY294002 reduced Akt and GSK3beta phosphorylation and increased brain injury after SAH. The present study suggests that the Akt/GSK3beta pathway might be involved in neuronal survival in acute brain injury after SAH.