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(Stroke. 2006;37:2140.)
© 2006 American Heart Association, Inc.

Original Contributions

Akt/GSK3ß Survival Signaling Is Involved in Acute Brain Injury After Subarachnoid Hemorrhage in Rats

Hidenori Endo, MD; Chikako Nito, MD, PhD; Hiroshi Kamada, MD, PhD; Fengshan Yu, MD Pak H. Chan, PhD

From the Department of Neurosurgery, Department of Neurology and Neurological Sciences, and the Program in Neurosciences, Stanford University School of Medicine, Stanford, Calif.

Correspondence to Dr Pak H. Chan, Neurosurgical Laboratories, Stanford University, 1201 Welch Rd, MSLS #P314, Stanford, CA 94305-5487. E-mail phchan{at}stanford.edu

Background and Purpose— Apoptotic cell death is associated with acute brain injury after subarachnoid hemorrhage (SAH). The Akt/glycogen synthase kinase-3ß (GSK3ß) 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.

Methods— We used an endovascular perforation model of SAH in rats. Phospho-Akt and phospho-GSK3ß 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/GSK3ß pathway in the phosphoinositide 3-kinase pathway after SAH.

Results— Phosphorylation of Akt and GSK3ß 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 GSK3ß phosphorylation and increased brain injury after SAH.

Conclusions— The present study suggests that the Akt/GSK3ß pathway might be involved in neuronal survival in acute brain injury after SAH.

Key Words: apoptosis • brain injuries • subarachnoid hemorrhage

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