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

  • Mutsumi Fujii
  • Sheng Chen
  • Damon Klebe
  • Yoshiteru Soejima
  • Alexander Vakhmyanin
  • John H. Zhang
Chapter
Part of the Springer Series in Translational Stroke Research book series (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.

Keywords

Nitric Oxide Basilar Artery Cerebral Vasospasm Early Brain Injury Angiographic Vasospasm 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

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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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Mutsumi Fujii
    • 1
  • Sheng Chen
    • 1
  • Damon Klebe
    • 1
  • Yoshiteru Soejima
    • 1
  • Alexander Vakhmyanin
    • 1
  • John H. Zhang
    • 2
  1. 1.Department of PhysiologyLoma Linda UniversityLoma LindaUSA
  2. 2.Department of Physiology, Pharmacology, and NeurosurgeryLoma Linda UniversityLoma LindaUSA

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