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Endothelial Cell Dysfunction and Injury in Subarachnoid Hemorrhage

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Abstract

In the brain, vascular endothelial cells conserve blood viscosity, control blood flow, and form the interface between central nervous system and circulating blood. Clinical outcome after aneurysmal subarachnoid hemorrhage is linked to early brain injury, cerebral vasospasm, and other causes of delayed cerebral ischemia. The cerebral vasculature remains a unique target for therapies since it becomes rapidly disrupted after subarachnoid hemorrhage, and damage to the blood vessels continues into the delayed injury phase. The current failure of therapies to improve clinical outcome warrants a re-evaluation of current therapeutic approaches. The mechanisms of endothelial cell injury and blood–brain barrier breakdown are critical to the pathway of cerebral injury, and an improved understanding of these mechanisms may lead to novel therapeutic targets. This review provides an update on the current understanding of endothelial cell injury following aneurysmal subarachnoid hemorrhage, including blood–brain barrier dysfunction.

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Acknowledgments

This work was supported by the University of Texas Health Science Center and AHA career development grant 18CDA34110036.

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Authors and Affiliations

  1. The Vivian L. Smith Department of Neurosurgery, University of Texas Health Science Center, 6431 Fannin St., Houston, TX, 77030, USA

    T. Peeyush Kumar, Devin W. McBride, Kanako Matsumura, Alba Rubi & Spiros L. Blackburn

  2. Department of Neurobiology and Anatomy, McGovern Medical School, Houston, TX, 77225, USA

    Pramod K. Dash

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  1. T. Peeyush Kumar
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  2. Devin W. McBride
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  3. Pramod K. Dash
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Correspondence to T. Peeyush Kumar.

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Review criteria

This review was based on searches of the PubMed database using each of the terms “Subarachnoid Hemorrhage” and “SAH,” in combination with the terms “endothelial cell,” “early brain injury” or “EBI,” “apoptosis,” “blood–brain barrier” or “BBB,” “cerebral vasospasm” or “CV,” “Inflammation,” and “microthrombosis.” No time limit was set with regard to publication date. Only English-language articles were retrieved. Appropriate articles were selected based on abstract review. Full articles were subsequently acquired and their references were searched for further appropriate material.

Key Points

• Aneurysmal subarachnoid hemorrhage (aSAH) can cause early and delayed brain injury.

• Few accepted therapeutic strategies are available for improving poor outcome in the treatment of aSAH. Current treatment strategies aimed at rescuing cerebral vasospasm do not improve outcome.

• Endothelial cell injury/dysfunction during early phase injury can play a critical role in the in SAH complications.

• The blood–brain barrier (BBB) protects the central nervous system from neurotoxic plasma components, blood cells, and pathogens present in the systemic circulation.

• Experimental studies have shown that post aSAH, multiple factors contribute to BBB breakdown that can facilitate inflammatory and immune responses contributing to poor outcome.

• Advancement of basic and clinical research directed to rescue endothelial cell injury and protect and restore BBB function following aSAH might provide novel targets for clinical intervention.

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Peeyush Kumar, T., McBride, D.W., Dash, P.K. et al. Endothelial Cell Dysfunction and Injury in Subarachnoid Hemorrhage. Mol Neurobiol 56, 1992–2006 (2019). https://doi.org/10.1007/s12035-018-1213-7

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