benzyloxycarbonylvalyl-alanyl-aspartyl-fluoromethyl-ketone and Brain-Edema

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.. 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.. 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.. 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.

Topics: Amino Acid Chloromethyl Ketones; Animals; Apoptosis; Blood-Brain Barrier; Brain Edema; Caspase 3; Caspases; Disease Models, Animal; Male; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Subarachnoid Hemorrhage