Neurovascular protection reduces early brain injury after subarachnoid hemorrhage.
OBJECTIVE
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.
Department of Neurosurgery, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA.
S
S
Park
M
M
Yamaguchi
C
C
Zhou
J W
JW
Calvert
J
J
Tang
John H
JH
Zhang
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier; D001929:Brain Edema; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000473:pathology*
D000590:Amino Acid Chloromethyl Ketones; D018696:Neuroprotective Agents; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases