The Role of the Glycocalyx in the Pathophysiology of Subarachnoid Hemorrhage-Induced Delayed Cerebral Ischemia

The glycocalyx is an important constituent of blood vessels located between the bloodstream and the endothelium. It plays a pivotal role in intercellular interactions in neuroinflammation, reduction of vascular oxidative stress, and provides a barrier regulating vascular permeability. In the brain, the glycocalyx is closely related to functions of the blood-brain barrier and neurovascular unit, both responsible for adequate neurovascular responses to potential threats to cerebral homeostasis. An aneurysmal subarachnoid hemorrhage (aSAH) occurs following rupture of an intracranial aneurysm and leads to immediate brain damage (early brain injury). In some cases, this can result in secondary brain damage, also known as delayed cerebral ischemia (DCI). DCI is a life-threatening condition that affects up to 30% of all aSAH patients. As such, it is associated with substantial societal and healthcare-related costs. Causes of DCI are multifactorial and thought to involve neuroinflammation, oxidative stress, neuroinflammation, thrombosis, and neurovascular uncoupling. To date, prediction of DCI is limited, and preventive and effective treatment strategies of DCI are scarce. There is increasing evidence that the glycocalyx is disrupted following an aSAH, and that glycocalyx disruption could precipitate or aggravate DCI. This review explores the potential role of the glycocalyx in the pathophysiological mechanisms contributing to DCI following aSAH. Understanding the role of the glycocalyx in DCI could advance the development of improved methods to predict DCI or identify patients at risk for DCI. This knowledge may also alter the methods and timing of preventive and treatment strategies of DCI. To this end, we review the potential and limitations of methods currently used to evaluate the glycocalyx, and strategies to restore or prevent glycocalyx shedding.

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Role of Endothelin-1 in Human Aneurysmal Subarachnoid Hemorrhage: Associations with Vasospasm and Delayed Cerebral Ischemia

Neurocritical Care ◽

10.1007/s12028-011-9508-9 ◽

2011 ◽

Vol 15 (1) ◽

pp. 19-27 ◽

Cited By ~ 30

Author(s):

Bhavani P. Thampatty ◽

Paula R. Sherwood ◽

Matthew J. Gallek ◽

Elizabeth A. Crago ◽

Dianxu Ren ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Endothelin 1

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The Role of the Blood Neutrophil-to-Lymphocyte Ratio in Aneurysmal Subarachnoid Hemorrhage

Frontiers in Neurology ◽

10.3389/fneur.2021.671098 ◽

2021 ◽

Vol 12 ◽

Author(s):

Lingxin Cai ◽

Hanhai Zeng ◽

Xiaoxiao Tan ◽

Xinyan Wu ◽

Cong Qian ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Critical Role ◽

Delayed Cerebral Ischemia ◽

Early Brain Injury ◽

Neutrophil To Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Novel Therapeutic Strategies ◽

Improved Accuracy

Aneurysmal subarachnoid hemorrhage (aSAH) is an important type of stroke with the highest rates of mortality and disability. Recent evidence indicates that neuroinflammation plays a critical role in both early brain injury and delayed neural deterioration after aSAH, contributing to unfavorable outcomes. The neutrophil-to-lymphocyte ratio (NLR) is a peripheral biomarker that conveys information about the inflammatory burden in terms of both innate and adaptive immunity. This review summarizes relevant studies that associate the NLR with aSAH to evaluate whether the NLR can predict outcomes and serve as an effective biomarker for clinical management. We found that increased NLR is valuable in predicting the clinical outcome of aSAH patients and is related to the risk of complications such as delayed cerebral ischemia (DCI) or rebleeding. Combined with other indicators, the NLR provides improved accuracy for predicting prognosis to stratify patients into different risk categories. The underlying pathophysiology is highlighted to identify new potential targets for neuroprotection and to develop novel therapeutic strategies.

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Targeting High Mobility Group Box 1 in Subarachnoid Hemorrhage: A Systematic Review

International Journal of Molecular Sciences ◽

10.3390/ijms21082709 ◽

2020 ◽

Vol 21 (8) ◽

pp. 2709 ◽

Cited By ~ 1

Author(s):

Sajjad Muhammad ◽

Shafqat Rasul Chaudhry ◽

Ulf Dietrich Kahlert ◽

Martin Lehecka ◽

Miikka Korja ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Brain Damage ◽

Molecular Mechanisms ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

High Mobility ◽

High Mobility Group ◽

Endovascular Coiling ◽

Pharmacological Interventions

Aneurysmal subarachnoid hemorrhage (aSAH) is a complex and potentially deadly disease. Neurosurgical clipping or endovascular coiling can successfully obliterate ruptured aneurysms in almost every case. However, despite successful interventions, the clinical outcomes of aSAH patients are often poor. The reasons for poor outcomes are numerous, including cerebral vasospasm (CVS), post-hemorrhagic hydrocephalus, systemic infections and delayed cerebral ischemia. Although CVS with subsequent cerebral ischemia is one of the main contributors to brain damage after aSAH, little is known about the underlying molecular mechanisms of brain damage. This review emphasizes the importance of pharmacological interventions targeting high mobility group box 1 (HMGB1)-mediated brain damage after subarachnoid hemorrhage (SAH) and CVS. We searched Pubmed, Ovid medline and Scopus for “subarachnoid hemorrhage” in combination with “HMGB1”. Based on these criteria, a total of 31 articles were retrieved. After excluding duplicates and selecting the relevant references from the retrieved articles, eight publications were selected for the review of the pharmacological interventions targeting HMGB1 in SAH. Damaged central nervous system cells release damage-associated molecular pattern molecules (DAMPs) that are important for initiating, driving and sustaining the inflammatory response following an aSAH. The discussed evidence suggested that HMGB1, an important DAMP, contributes to brain damage during early brain injury and also to the development of CVS during the late phase. Different pharmacological interventions employing natural compounds with HMGB1-antagonizing activity, antibody targeting of HMGB1 or scavenging HMGB1 by soluble receptors for advanced glycation end products (sRAGE), have been shown to dampen the inflammation mediated brain damage and protect against CVS. The experimental data suggest that HMGB1 inhibition is a promising strategy to reduce aSAH-related brain damage and CVS. Clinical studies are needed to validate these findings that may lead to the development of potential treatment options that are much needed in aSAH.

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Role of ABO blood type in delayed cerebral ischemia onset and clinical outcomes after aneurysmal subarachnoid hemorrhage in an ethnic minority urban population

Surgical Neurology International ◽

10.25259/sni_10_2020 ◽

2020 ◽

Vol 11 ◽

pp. 108

Author(s):

Santiago René Unda ◽

Tarini Vats ◽

Rafael De la Garza Ramos ◽

Phillip Cezaryirli ◽

David J. Altschul

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Clinical Outcomes ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Univariate Analysis ◽

Delayed Cerebral Ischemia ◽

Blood Type ◽

Academic Center ◽

Abo Blood Type

Background: In recent years, the role of ABO blood type moved into focus through the discovery of different hemostaseologic properties with importance in many diseases including subarachnoid hemorrhage (SAH). However, the role of ABO blood type in delayed cerebral ischemia (DCI) onset, clinical progress, and outcome after SAH is to date largely unexplored. Our aim was to explore the role of ABO blood group in DCI and clinical outcomes after aneurysmal SAH (aSAH). Methods: A retrospective analysis was made with data collected from patients who presented aSAH at our single- academic center from 2015 to 2018. We included demographic, clinical, and imaging variables in the univariate analysis and in the subsequent multivariate analysis. Results: A total of 204 patients were included in this study. About 17.9% of “O” type patients developed a DCI while DCI was reported in only 8.2% of non-O type patients (P = 0.04). “O” type was an independent risk after in the logistic regression after adjusting for significant factors in the univariate analysis (OR=2.530, 95% CI: 1.040- 6.151, P = 0.41). Compared to “non-O” type patients, “O” type patients had a trend to have poorer outcomes at discharge (25.5% vs. 21.3%, P = 0.489) and at 12–18 months (21.1% vs. 19.5%, P = 0.795). However, there were no significant differences. Conclusion: Our study evidenced that patients with “O” blood type have higher risk of DCI onset after aSAH. Although these findings need to be confirmed, they may aid to improve DCI prevention and outcome predictions.

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