Microvascular protection is essential for successful neuroprotection in stroke

Gursoy-Ozdemir Y., Yemisci M., DALKARA T.

JOURNAL OF NEUROCHEMISTRY, vol.123, pp.2-11, 2012 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Review
  • Volume: 123
  • Publication Date: 2012
  • Doi Number: 10.1111/j.1471-4159.2012.07938.x
  • Journal Name: JOURNAL OF NEUROCHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.2-11
  • Keywords: cerebral ischemia, nitric oxide, neurovascular unit, no-reflow, peroxynitrite, pericyte, FOCAL CEREBRAL-ISCHEMIA, BLOOD-BRAIN-BARRIER, NITRIC-OXIDE SYNTHASE, SCANNING CONFOCAL MICROSCOPY, TISSUE-PLASMINOGEN ACTIVATOR, EVALUATION TRIAL EPITHET, OXIDATIVE STRESS, NADPH OXIDASE, MICROCIRCULATORY OBSTRUCTION, HEMORRHAGIC TRANSFORMATION
  • Hacettepe University Affiliated: Yes

Abstract

Currently, the best way of neuroprotection for acute ischemic stroke appears to be restoration of blood flow to the ischemic area by thrombolysis. Unfortunately, a short therapeutic time window as well as thrombolysis-induced bleeding and edema limit the use of recanalization therapies. Here, we review the evidence suggesting that ischemia/reperfusion-induced microvascular injury plays a critical role in determining tissue survival after recanalization in focal cerebral ischemia by disrupting the bloodbrain barrier integrity and promoting microcirculatory clogging. Among many complex mechanisms of the ischemiareperfusion injury, overproduction of oxygen and nitrogen radicals on the microvascular wall appears to significantly contribute to these pathological processes. These developments bring about the exciting possibility that effective suppression of oxidative/nitrative stress during pharmacological or interventional re-opening of the occluded artery may significantly improve the outcome of recanalization therapies in stroke patients by improving microcirculatory reflow as well as by preventing hemorrhagic conversion and vasogenic edema. They also point to the critical (but partly neglected) importance of the microcirculation in neuroprotection.