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Identifying Vascular Targets to Treat Hemorrhagic Stroke

Chapter
Part of the Springer Series in Translational Stroke Research book series (SSTSR)

Abstract

Hemorrhagic stroke is a devastating type of stroke that affects 20% of all stroke patients. In spite of the severity of morbidity and the high rate of mortality associated with hemorrhagic stroke, current treatment methods are quite insufficient to reduce long-term morbidity and high mortality rate, up to 50%, associated with bleeding into critical brain structures, the ventricles, and the subarachnoid space. Preclinical and translational research programs have led to significant advances in the understanding of important mechanisms that contribute to cell death and clinical deficits. The most important findings revolve around a key set of basic mechanisms intimately involved in brain bleeding, including activation of matrix membrane metalloproteinases (MMP), specifically MMP-2 and MMP-9, enhanced free radical production and oxidative stress, and both altered inflammatory and coagulation pathways. It is now becoming apparent and accepted that brain bleeding may result in the activation of a “hemorrhagic stroke cascade” in many cell types including neurons, glia, and vasculature. Moreover, in hemorrhage there is also activation of many components of the “ischemic stroke cascade.” The activation of multiple hemorrhage and ischemia pathways is a two-edged sword: it results in the activation of series of detrimental pathways, some of which are duplicated in each cascade, but they may allow for useful pharmacological intervention.

Because there is parallel or simultaneous activation of pathways, future therapies may have to rely on combining drugs or pleiotropic compounds with multi-target activities. This chapter will comprehensively review some of the possible targets for pharmacological intervention as well as address some new approaches to induce metabolic downregulation or inhibition of multiple pathways, with the goal of clinical improvement.

Keywords

Brain Edema Hemorrhagic Stroke Heme Oxygenase Cerebral Amyloid Angiopathy Hemorrhagic Transformation 
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 article was supported by a U01 Translational research grant NS060685 to PAL.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of NeurologyCedars-Sinai Medical CenterLos AngelesUSA

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