Published Online
on August 19, 2004

A more recent version of this article appeared on October 1, 2004

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Submitted on May 5, 2004
Revised on July 20, 2004
Accepted on July 21, 2004

Neurovascular Protection Reduces Early Brain Injury After Subarachnoid Hemorrhage

S. Park MS; M. Yamaguchi MD; C. Zhou MD, PhD; J. W. Calvert BS; J. Tang MD; and John H. Zhang MD, PhD^*

From the Departments of Neurosurgery (M.Y., C.Z., J.W.C., J.H.Z.) and Molecular and Cellular Physiology (J.T., J.H.Z.), Louisiana State University Health Sciences Center, Shreveport.

^* To whom correspondence should be addressed. E-mail: johnzhang3910{at}yahoo.com.

Background and Purpose--Cell death, especially apoptosis, occurred in brain tissues after subarachnoid hemorrhage (SAH). We examined the relationships between apoptosis and the disruption of blood-brain barrier (BBB), brain edema, and mortality in an established endovascular perforation model in male Sprague-Dawley rats.

Methods--A pan-caspase inhibitor (z-VAD-FMK) was administered intraperitoneally at 1 hour before and 6 hours after SAH. Expression of caspase-3 and positive TUNEL was examined as markers for apoptosis.

Results--Apoptosis occurred mostly in cerebral endothelial cells, partially in neurons in the hippocampus, and to a lesser degree in the cerebral cortex. Accordingly, increased BBB permeability and brain water content were observed, accompanied by neurological deficit and a high mortality at 24 hours after SAH. z-VAD-FMK suppressed TUNEL and caspase-3 staining in endothelial cells, decreased caspase-3 activation, reduced BBB permeability, relieved vasospasm, abolished brain edema, and improved neurological outcome.

Conclusions--The major effect of z-VAD-FMK on early brain injury after SAH was probably neurovascular protection of cerebral endothelial cells, which results in less damage on BBB.

Key words: apoptosis • blood-brain barrier • brain edema • subarachnoid hemorrhage

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