Molecular Neurobiology

, Volume 41, Issue 2, pp 172–179

Reperfusion and Neurovascular Dysfunction in Stroke: from Basic Mechanisms to Potential Strategies for Neuroprotection

Authors

  • Joo Eun Jung
    • Department of NeurosurgeryStanford University School of Medicine
    • Department of Neurology and Neurological SciencesStanford University School of Medicine
    • Program in NeurosciencesStanford University School of Medicine
  • Gab Seok Kim
    • Department of NeurosurgeryStanford University School of Medicine
    • Department of Neurology and Neurological SciencesStanford University School of Medicine
    • Program in NeurosciencesStanford University School of Medicine
  • Hai Chen
    • Department of NeurosurgeryStanford University School of Medicine
    • Department of Neurology and Neurological SciencesStanford University School of Medicine
    • Program in NeurosciencesStanford University School of Medicine
  • Carolina M. Maier
    • Department of NeurosurgeryStanford University School of Medicine
    • Department of Neurology and Neurological SciencesStanford University School of Medicine
    • Program in NeurosciencesStanford University School of Medicine
  • Purnima Narasimhan
    • Department of NeurosurgeryStanford University School of Medicine
    • Department of Neurology and Neurological SciencesStanford University School of Medicine
    • Program in NeurosciencesStanford University School of Medicine
  • Yun Seon Song
    • Department of NeurosurgeryStanford University School of Medicine
    • Department of Neurology and Neurological SciencesStanford University School of Medicine
    • Program in NeurosciencesStanford University School of Medicine
  • Kuniyasu Niizuma
    • Department of NeurosurgeryStanford University School of Medicine
    • Department of Neurology and Neurological SciencesStanford University School of Medicine
    • Program in NeurosciencesStanford University School of Medicine
  • Masataka Katsu
    • Department of NeurosurgeryStanford University School of Medicine
    • Department of Neurology and Neurological SciencesStanford University School of Medicine
    • Program in NeurosciencesStanford University School of Medicine
  • Nobuya Okami
    • Department of NeurosurgeryStanford University School of Medicine
    • Department of Neurology and Neurological SciencesStanford University School of Medicine
    • Program in NeurosciencesStanford University School of Medicine
  • Hideyuki Yoshioka
    • Department of NeurosurgeryStanford University School of Medicine
    • Department of Neurology and Neurological SciencesStanford University School of Medicine
    • Program in NeurosciencesStanford University School of Medicine
  • Hiroyuki Sakata
    • Department of NeurosurgeryStanford University School of Medicine
    • Department of Neurology and Neurological SciencesStanford University School of Medicine
    • Program in NeurosciencesStanford University School of Medicine
  • Christina E. Goeders
    • Department of NeurosurgeryStanford University School of Medicine
    • Department of Neurology and Neurological SciencesStanford University School of Medicine
    • Program in NeurosciencesStanford University School of Medicine
    • Department of NeurosurgeryStanford University School of Medicine
    • Department of Neurology and Neurological SciencesStanford University School of Medicine
    • Program in NeurosciencesStanford University School of Medicine
Article

DOI: 10.1007/s12035-010-8102-z

Cite this article as:
Jung, J.E., Kim, G.S., Chen, H. et al. Mol Neurobiol (2010) 41: 172. doi:10.1007/s12035-010-8102-z

Abstract

Effective stroke therapies require recanalization of occluded cerebral blood vessels. However, reperfusion can cause neurovascular injury, leading to cerebral edema, brain hemorrhage, and neuronal death by apoptosis/necrosis. These complications, which result from excess production of reactive oxygen species in mitochondria, significantly limit the benefits of stroke therapies. We have developed a focal stroke model using mice deficient in mitochondrial manganese-superoxide dismutase (SOD2−/+) to investigate neurovascular endothelial damage that occurs during reperfusion. Following focal stroke and reperfusion, SOD2−/+ mice had delayed blood-brain barrier breakdown, associated with activation of matrix metalloproteinase and high brain hemorrhage rates, whereas a decrease in apoptosis and hemorrhage was observed in SOD2 overexpressors. Thus, induction and activation of SOD2 is a novel strategy for neurovascular protection after ischemia/reperfusion. Our recent study identified the signal transducer and activator of transcription 3 (STAT3) as a transcription factor of the mouse SOD2 gene. During reperfusion, activation of STAT3 and its recruitment into the SOD2 gene were blocked, resulting in increased oxidative stress and neuronal apoptosis. In contrast, pharmacological activation of STAT3 induced SOD2 expression, which limits ischemic neuronal death. Our studies point to antioxidant-based neurovascular protective strategies as potential treatments to expand the therapeutic window of currently approved therapies.

Keywords

Cerebral ischemiaOxidative stressReactive oxygen speciesMitochondriaMn-SODSTAT3NADPH oxidaseCK2Neuroprotective signaling

Copyright information

© The Author(s) 2010