Transition of research focus from vasospasm to early brain injury after subarachnoid hemorrhage

• Published in: Journal of neurochemistry Vol. 123; no. s2; pp. 12 - 21
• Main Authors: Caner, Basak, Hou, Jack, Altay, Orhan, Fuj ii, Mutsumi, Zhang, John H.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-11-2012
• Subjects: Blood vessels; Blood-Brain Barrier - physiopathology; Brain damage; Brain Injuries - etiology; Brain Injuries - therapy; Cell Death; Cerebrovascular Circulation - physiology; Clinical Trials as Topic - methods; delayed ischemic neurological deficit; early brain injury; Hemorrhage; Humans; Inflammation - etiology; Intracranial Pressure; Neurochemistry; Oxidative Stress; Pharmacology; subarachnoid hemorrhage; Subarachnoid Hemorrhage - complications; vasospasm; Vasospasm, Intracranial - etiology; Vasospasm, Intracranial - therapy
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2012.07939.x

Subarachnoid hemorrhage is a devastating disease that can be difficult to manage. Not only is the initial bleeding and rebleeding associated with high mortality, but a large fraction of patients also develop a delayed neurological deficit even when the aneurysm was successfully secured with clipping or coiling. Past research effort has traditionally been focused on vasospasm, which was conceived to be the sole factor for delayed neurological deficit. The failure of anti‐vasospastic drugs to improve outcome in clinical trials has brought into focus the significance of early brain injury. The immediate events associated with subarachnoid hemorrhage, including increased intracranial pressure, decreased cerebral blood flow and global ischemia initiate a cascade of pathological changes that occur before the onset of delayed vasospasm. These pathological changes in the very early stage of the hemorrhage propagate and cause blood–brain barrier disruption, inflammation, oxidative stress and cell death. Focusing only on the treatment of vasospasm with complete disregard for early brain injury is insufficient for the management of subarachnoid hemorrhage. Instead, a therapeutic intervention has to aim at stopping the molecular cascades of early brain injury that may lead to long‐term deficits in addition to vasospasm. We review the pathological mechanisms of early brain injury, which may reveal new therapeutic avenues that can be exploited to serve as combination therapy with anti‐vasospasm medications in the future.