Blocking VEGF by Bevacizumab Attenuates VEGF-Induced Vasospasm After Experimental Subarachnoid Hemorrhage in Rabbits

Vasospasm after subarachnoid hemorrhage (SAH) plays a vital role in the development of delayed cerebral ischemia. Anti- vascular endothelial growth factor (VEGF) antibodies, like bevacizumab (BEV), may attenuate VEGF-stimulated angiogenesis, reduced vascular cell proliferation, and improve vasospasm after SAH.

Thirty-two adult male New Zealand white rabbits were randomly divided into 4 groups of 8 rabbits in each group: group 1 (control); group 2 (SAH); group 3 (SAH + vehicle); and group 4 (SAH + BEV). BEV (5 mg/kg, intraperitoneally) was administered 5 minutes after the intracisternal blood injection and continued for 72 hours once per day in the same dose for group 4. Animals were sacrificed 72 hours after SAH. Basilar artery cross-sectional areas, arterial wall thicknesses, and hippocampal degeneration scores were evaluated in all groups.

VEGF is associated with the narrowing of the basilar artery. Treatment with BEV statistically significantly increased the cross-sectional area of the basilar artery when compared with the SAH and the vehicle groups. Basilar artery wall thicknesses in the BEV group was statistically significant smaller than in the SAH and vehicle groups. The hippocampal degeneration scores for the BEV and control groups were similar and significantly lower than those for the SAH and vehicle groups.

Cellular proliferation and subsequent vessel wall thickening is a reason to delay cerebral ischemia and deterioration of the neurocognitive function. Intraperitoneal administration of BEV was found to attenuate cerebral vasospasm and prevent delayed cerebral ischemia and improve neurocognitive function after SAH in rabbits.