Signaling Pathways for Early Brain Injury after Subarachnoid Hemorrhage

TLDR

Few studies have examined the signaling pathways that contribute to early brain injury after subarachnoid hemorrhage (SAH). The study investigates the role of VEGF and MAPK signaling in early brain injury following SAH in a rat model. Using 172 male Sprague‑Dawley rats, SAH was induced by arterial puncture, and 24‑hour outcomes—BBB integrity, edema, intracranial pressure, mortality—and phosphorylation of VEGF and MAPK subgroups were assessed in cortex and arteries. SAH elevated intracranial pressure, BBB permeability, edema, and mortality; phosphorylation of VEGF and MAPKs increased, and Src‑family kinase inhibition with PP1 reduced these effects, supporting VEGF‑MAPK as therapeutic targets.

Abstract

Few studies have examined the signaling pathways that contribute to early brain injury after subarachnoid hemorrhage (SAH). Using a rat SAH model, the authors explored the role of vascular endothelial growth factor (VEGF) and mitogen-activation protein kinase (MAPK) in early brain injury. Male Sprague-Dawley rats (n = 172) weighing 300 to 350 g were used for the experimental SAH model, which was induced by puncturing the bifurcation of the left anterior cerebral and middle cerebral arteries. The blood–brain barrier (BBB), brain edema, intracranial pressure, and mortality were evaluated at 24 hours after SAH. The phosphorylation of VEGF and different MAPK subgroups (ERK1/2, p38, and JNK) were examined in both the cortex and the major cerebral arteries. Experimental SAH increased intracranial pressure, BBB permeability, and brain edema and produced high mortality. SAH induced phosphorylation of VEGF and MAPKs in the cerebral arteries and, to a lesser degree, in the cortex. PP1, an Src-family kinase inhibitor, reduced BBB permeability, brain edema, and mortality and decreased the phosphorylation of VEGF and MAPKs. The authors conclude that VEGF contributes to early brain injury after SAH by enhancing the activation of the MAPK pathways, and that the inhibition of these pathways might offer new treatment strategies for SAH.