Early brain injury, an evolving frontier in subarachnoid hemorrhage research

Abstract

Subarachnoid hemorrhage (SAH), predominantly caused by a ruptured aneurysm, is a devastating neurological disease that has a morbidity and mortality rate higher than 50%. Most of the traditional in vivo research has focused on the pathophysiological or morphological changes of large-arteries after intracisternal blood injection. This was due to a widely held assumption that delayed vasospasm following SAH was the major cause of delayed cerebral ischemia and poor outcome. However, the results of the CONSCIOUS-1 trial implicated some other pathophysiological factors, independent of angiographic vasospasm, in contributing to the poor clinical outcome. The term early brain injury (EBI) has been coined and describes the immediate injury to the brain after SAH, before onset of delayed vasospasm. During the EBI period, a ruptured aneurysm brings on many physiological derangements such as increasing intracranial pressure (ICP), decreased cerebral blood flow (CBF), and global cerebral ischemia. These events initiate secondary injuries such as blood-brain barrier disruption, inflammation, and oxidative cascades that all ultimately lead to cell death. Given the fact that the reversal of vasospasm does not appear to improve patient outcome, it could be argued that the treatment of EBI may successfully attenuate some of the devastating secondary injuries and improve the outcome of patients with SAH. In this review, we provide an overview of the major advances in EBI after SAH research.

Keywords: Animal model; Cerebral vasospasm; Early brain injury; Subarachnoid hemorrhage.

Figure 1

Comparison of subarachnoid hemorrhage in human and experimental endovascular perforation model of rat: (A) normal brain computed tomography (CT) scan in human around the circle of Willis, (B) a photograph of a sham-operated rat after cardiac perfusion, (C) high density area in the basal cistern on the CT scan after subarachnoid hemorrhage in human, (D) the cause of subarachnoid hemorrhage was an ruptured aneurysm in human (arrow), and (E) subarachnoid hemorrhage at the ventral surface induced by the endovascular perforation of the internal carotid artery in rat.

Figure 2

Mechanism of early brain injury after SAH: SAH causes acute global ischemia, altered ionic homeostasis, degradation of vascular integrity, and molecular alterations, all leading to cell death.