TY - JOUR
T1 - Conditioning-based therapeutics for aneurysmal subarachnoid hemorrhage – A critical review
AU - Pugazenthi, Sangami
AU - Norris, Aaron J.
AU - Lauzier, David C.
AU - Lele, Abhijit V.
AU - Huguenard, Anna
AU - Dhar, Rajat
AU - Zipfel, Gregory J.
AU - Athiraman, Umeshkumar
N1 - Publisher Copyright:
© The Author(s) 2023.
PY - 2024/3
Y1 - 2024/3
N2 - Aneurysmal subarachnoid hemorrhage (SAH) carries significant mortality and morbidity, with nearly half of SAH survivors having major cognitive dysfunction that impairs their functional status, emotional health, and quality of life. Apart from the initial hemorrhage severity, secondary brain injury due to early brain injury and delayed cerebral ischemia plays a leading role in patient outcome after SAH. While many strategies to combat secondary brain injury have been developed in preclinical studies and tested in late phase clinical trials, only one (nimodipine) has proven efficacious for improving long-term functional outcome. The causes of these failures are likely multitude, but include use of therapies targeting only one element of what has proven to be multifactorial brain injury process. Conditioning is a therapeutic strategy that leverages endogenous protective mechanisms to exert powerful and remarkably pleiotropic protective effects against injury to all major cell types of the CNS. The aim of this article is to review the current body of evidence for the use of conditioning agents in SAH, summarize the underlying neuroprotective mechanisms, and identify gaps in the current literature to guide future investigation with the long-term goal of identifying a conditioning-based therapeutic that significantly improves functional and cognitive outcomes for SAH patients.
AB - Aneurysmal subarachnoid hemorrhage (SAH) carries significant mortality and morbidity, with nearly half of SAH survivors having major cognitive dysfunction that impairs their functional status, emotional health, and quality of life. Apart from the initial hemorrhage severity, secondary brain injury due to early brain injury and delayed cerebral ischemia plays a leading role in patient outcome after SAH. While many strategies to combat secondary brain injury have been developed in preclinical studies and tested in late phase clinical trials, only one (nimodipine) has proven efficacious for improving long-term functional outcome. The causes of these failures are likely multitude, but include use of therapies targeting only one element of what has proven to be multifactorial brain injury process. Conditioning is a therapeutic strategy that leverages endogenous protective mechanisms to exert powerful and remarkably pleiotropic protective effects against injury to all major cell types of the CNS. The aim of this article is to review the current body of evidence for the use of conditioning agents in SAH, summarize the underlying neuroprotective mechanisms, and identify gaps in the current literature to guide future investigation with the long-term goal of identifying a conditioning-based therapeutic that significantly improves functional and cognitive outcomes for SAH patients.
KW - Conditioning strategies
KW - delayed cerebral ischemia
KW - early brain injury
KW - neurologic outcomes
KW - neurovascular protection
KW - subarachnoid hemorrhage
UR - http://www.scopus.com/inward/record.url?scp=85177872305&partnerID=8YFLogxK
U2 - 10.1177/0271678X231218908
DO - 10.1177/0271678X231218908
M3 - Review article
C2 - 38017387
AN - SCOPUS:85177872305
SN - 0271-678X
VL - 44
SP - 317
EP - 332
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
IS - 3
ER -