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Inflammation as a Therapeutic Target after Subarachnoid Hemorrhage: Advances and Challenges

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Immunological Mechanisms and Therapies in Brain Injuries and Stroke

Part of the book series: Springer Series in Translational Stroke Research ((SSTSR,volume 6))

Abstract

Subarachnoid hemorrhage (SAH) results from the rupture of an intracranial aneurysm, and the first consequent events are increased intracranial pressure (ICP), reduced cerebral perfusion pressure (CPP), and decreased cerebral blood flow (CBF). The resultant hypoxic state alters autoregulation, ionic homeostasis, and excitotoxicity as well as initiates secondary injuries such as cytotoxic edema, blood-brain barrier (BBB) disruption, inflammation, and apoptotic cell death. Inflammation persists through hemorrhage degradation in the subarachnoid space. Several different aspects of the inflammatory response have been demonstrated in stroke pathogenesis, including cellular response (e.g., leukocyte adherence and microglia activation), expression of adhesion molecules (e.g., selectins, integrins, and immunoglobulin superfamily), production of inflammatory mediators (e.g., cytokines, nitric oxide/nitric oxide synthase (NO/NOS), and free radicals), and accumulation of platelet aggregates. Since all of these inflammatory aspects lead to brain edema and cell death, inflammation could be a particularly important target for designing therapeutic strategies against secondary injuries after SAH. Given these inflammatory contributions could be seen in large vessels, a plethora of research has been intended to reduce cerebral vasospasm (CVS) after SAH. The main research field, however, is moving toward studying early brain injury (EBI) because some human research demonstrated the morphological alleviation of CVS alone might not improve the functional recovery in patients after SAH. This chapter provides the current knowledge of the inflammatory response, translational research, and human clinical trials in SAH as well as discusses emerging opportunities for novel therapeutic strategies for clinical management of SAH.

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Acknowledgments

This study was supports by the National Institutes of Health NS053407 to J.H. Zhang.

Conflict of Interest Statement

We declare that we have no conflicts of interest.

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Authors and Affiliations

  1. Department of Physiology, Loma Linda University, Loma Linda, CA, USA

    Mutsumi Fujii, Sheng Chen, Damon Klebe, Yoshiteru Soejima & Alexander Vakhmyanin

  2. Department of Physiology, Pharmacology, and Neurosurgery, Loma Linda University, Loma Linda, CA, USA

    John H. Zhang

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  1. Mutsumi Fujii
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  2. Sheng Chen
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  3. Damon Klebe
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  4. Yoshiteru Soejima
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Correspondence to John H. Zhang .

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  1. University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

    Jun Chen

  2. Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

    Xiaoming Hu

  3. Molecular Microbiology & Immunology, Oregon Health & Sciences University, Portland, Oregon, USA

    Mary Stenzel-Poore

  4. Loma Linda University, Loma Linda, California, USA

    John H. Zhang

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Fujii, M., Chen, S., Klebe, D., Soejima, Y., Vakhmyanin, A., Zhang, J.H. (2014). Inflammation as a Therapeutic Target after Subarachnoid Hemorrhage: Advances and Challenges. In: Chen, J., Hu, X., Stenzel-Poore, M., Zhang, J. (eds) Immunological Mechanisms and Therapies in Brain Injuries and Stroke. Springer Series in Translational Stroke Research, vol 6. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8915-3_14

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