Neurovascular protection reduces early brain injury after subarachnoid hemorrhage

  • Stroke. 2004 Oct;35(10):2412-7. doi: 10.1161/01.STR.0000141162.29864.e9.
S Park  1 ,  M Yamaguchi ,  C Zhou ,  J W Calvert ,  J Tang ,  John H Zhang
Affiliations
  • 1. Department of Neurosurgery, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA.
PMID: 15322302 DOI: 10.1161/01.STR.0000141162.29864.e9
Abstract

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.

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