Published online before print August 19, 2004, doi: 10.1161/01.STR.0000141162.29864.e9
(Stroke. 2004;35:2412.)
© 2004 American Heart Association, Inc.
Original Contributions |
Neurovascular Protection Reduces Early Brain Injury After Subarachnoid Hemorrhage
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, La.
Correspondence to Dr John H. Zhang, Department of Neurosurgery, Louisiana State University Health Sciences Center, 1501 Kings Highway, PO Box 33932, Shreveport, LA 71130-3932. 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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