Conditioning-based therapeutics for aneurysmal subarachnoid hemorrhage - A critical review

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:44

Enthalten in:

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism - 44(2024), 3 vom: 28. März, Seite 317-332

Sprache:

Englisch

Beteiligte Personen:

Pugazenthi, Sangami [VerfasserIn]
Norris, Aaron J [VerfasserIn]
Lauzier, David C [VerfasserIn]
Lele, Abhijit V [VerfasserIn]
Huguenard, Anna [VerfasserIn]
Dhar, Rajat [VerfasserIn]
Zipfel, Gregory J [VerfasserIn]
Athiraman, Umeshkumar [VerfasserIn]

Links:

Volltext

Themen:

57WA9QZ5WH
Conditioning strategies
Delayed cerebral ischemia
Early brain injury
Journal Article
Neurologic outcomes
Neurovascular protection
Nimodipine
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Subarachnoid hemorrhage

Anmerkungen:

Date Completed 16.02.2024

Date Revised 20.03.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1177/0271678X231218908

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM365085529