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Gelatinase-Mediated Impairment of Microvascular Beds in Cerebral Ischemia and Reperfusion Injury

  • Shanyan Chen
  • Hailong Song
  • Jiankun Cui
  • Joel I. Shenker
  • Yujie Chen
  • Grace Y. Sun
  • Hua Feng
  • Zezong Gu
Chapter
Part of the Springer Series in Translational Stroke Research book series (SSTSR)

Abstract

Stroke is one of the leading causes of death, and acute ischemic stroke (AIS) is the most common form. Tissue plasminogen activator (tPA) is the only FDA-approved drug for recanalization in AIS with narrow therapeutic window. In this chapter, we will discuss the activation of gelatinases (MMP-2/9), one of the major mediators in cerebral ischemia and reperfusion injury (CIRI) with exogenous tPA in AIS. First, we briefly overview the structure of microvascular beds and the homeostasis of neurovascular unit associated with the extracellular matrix (ECM). Then we review the gelatinase-mediated degradation of ECM and the impairment of microvascular beds in AIS. Moreover, we discuss the self-perpetuating loop of gelatinase activation in CIRI with exogenous tPA. At last, we literature available approaches showing protective functions through blocking the vicious circle of gelatinase activation, which may hold great promise in combined treatment with tPA in AIS.

Keywords

Gelatinases Microvascular beds Cerebral ischemia and reperfusion injury Extracellular matrix Mechanism-based inhibitor tPA 

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Shanyan Chen
    • 1
    • 2
  • Hailong Song
    • 1
    • 2
  • Jiankun Cui
    • 2
    • 3
  • Joel I. Shenker
    • 4
  • Yujie Chen
    • 5
  • Grace Y. Sun
    • 2
    • 6
  • Hua Feng
    • 5
  • Zezong Gu
    • 2
    • 3
  1. 1.Interdisciplinary Neuroscience ProgramUniversity of Missouri School of MedicineColumbiaUSA
  2. 2.Department of Pathology and Anatomical SciencesUniversity of Missouri School of MedicineColumbiaUSA
  3. 3.Harry S. Truman Memorial Veterans’ Hospital Research ServiceColumbiaUSA
  4. 4.Department of NeurologyUniversity of Missouri School of MedicineColumbiaUSA
  5. 5.Department of Neurosurgery, Southwest HospitalThird Military Medical UniversityChongqingChina
  6. 6.Department of BiochemistryUniversity of Missouri School of MedicineColumbiaUSA

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