Neurovascular Protection Reduces Early Brain Injury After Subarachnoid Hemorrhage

TLDR

Subarachnoid hemorrhage induces widespread cell death, particularly apoptosis, in brain tissues. The study aimed to investigate the role of apoptosis in early brain injury following subarachnoid hemorrhage. Using an endovascular perforation rat model, the authors administered the pan‑caspase inhibitor z‑VAD‑FMK and measured caspase‑3 and TUNEL activity to assess its effects on blood‑brain barrier integrity, brain edema, and mortality. z‑VAD‑FMK markedly reduced endothelial apoptosis, preserved BBB function, decreased brain edema, alleviated vasospasm, and improved neurological outcomes, demonstrating neurovascular protection as the principal mechanism of early brain injury attenuation after SAH.

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.