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Early Brain Injury, an Evolving Frontier in Subarachnoid Hemorrhage Research

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TLDR
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 and the reversal of vasospasm does not appear to improve patient outcome.
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.

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Journal ArticleDOI

Spontaneous subarachnoid haemorrhage

TL;DR: Challenges that remain relate to prevention of subarachnoid haemorrhage by improved screening and development of lower-risk methods to repair or stabilise aneurysms that have not yet ruptured and Multicentre cooperative efforts might increase the knowledge that can be gained from clinical trials.
Journal ArticleDOI

Delayed Cerebral Ischemia after Subarachnoid Hemorrhage: Beyond Vasospasm and Towards a Multifactorial Pathophysiology.

TL;DR: This review summarizes some of the main mechanisms under investigation including cerebral vascular dysregulation, microthrombosis, cortical spreading depolarizations, and neuroinflammation and provides evidence that additional mechanisms may play equal if not more important roles.
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Cerebrospinal fluid dynamics and intracranial pressure elevation in neurological diseases

TL;DR: Emerging evidence suggests that pharmacological targeting of aquaporins, transient receptor potential vanilloid type 4 (TRPV4), and the Na+–K+–2Cl− cotransporter (NKCC1) merit further investigation as potential targets in neurological diseases involving impaired brain fluid dynamics and elevated ICP.
References
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Journal ArticleDOI

Guidelines for the management of aneurysmal subarachnoid hemorrhage: A statement for healthcare professionals from a special writing group of the stroke council, American heart association

TL;DR: A systematic literature review was conducted based on a search of MEDLINE to identify all relevant randomized clinical trials published between June 30, 1994, and November 1, 2006 to reevaluate the recommendations for management of aneurysmal SAH.
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Cerebral vasospasm following aneurysmal subarachnoid hemorrhage.

TL;DR: Rheological or hemodynamic manipulations to prevent or reverse ischemic consequences of vasospasm are relatively effective, but complicated and hazardous, and should be viewed principally as interim measures awaiting development of more specific therapies for the arterial narrowing.
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Initial and recurrent bleeding are the major causes of death following subarachnoid hemorrhage.

TL;DR: Most deaths after subarachnoid hemorrhage occur very rapidly and are due to the initial hemorrhage, and rebleeding is the most important preventable cause of death in hospitalized patients.
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Clazosentan to overcome neurological ischemia and infarction occurring after subarachnoid hemorrhage (CONSCIOUS-1): randomized, double-blind, placebo-controlled phase 2 dose-finding trial.

TL;DR: Clazosentan significantly decreased moderate and severe vasospasms in a dose-dependent manner and showed a trend for reduction in vasospasm-related morbidity/mortality in patients with aneurysmal subarachnoid hemorrhage when centrally assessed.
Journal ArticleDOI

Mechanisms of early brain injury after subarachnoid hemorrhage

TL;DR: Experimental data suggest that the apoptotic cascades occur very early after the initial insult and may be related directly to physiologic sequela commonly associated with SAH.
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