Abstract
Early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (SAH) is the most influential clinical determinant of outcomes. Despite significant advances in understanding of the pathophysiology of EBI, currently no treatments to target EBI have been developed. This review summarizes recent advances in EBI research over the past five years with a focus on potential therapeutic targets. Mechanism-specific translational studies are converging on several pathophysiologic pathways: improved antioxidant delivery and the Sirt1/Nrf2 pathway for reactive oxygen species; NLRP3 inflammasome and microglial polarization for inflammation; and the PI3K/Akt pathway for apoptosis. Recently identified mechanistic components, such as microcirculatory failure and ferroptosis, need particular attention. Clinical studies developing radiographic markers and mechanism-specific, biofluid markers are attempting to bridge the translational therapeutic gap. There has been an exponential growth in EBI research. Further clinical studies which address specific pathophysiology mechanisms need to be performed to identify novel therapeutic approaches.
Published Version
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