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Differential Effects of Delta and Epsilon Protein Kinase C in Modulation of Postischemic Cerebral Blood Flow

  • Hung Wen Lin
  • David Della-Morte
  • John W. Thompson
  • Victoria L. Gresia
  • Srinivasan V. Narayanan
  • R. Anthony DeFazio
  • Ami P. Raval
  • Isabel Saul
  • Kunjan R. Dave
  • Kahlilia C. Morris
  • Min-Liang Si
  • Miguel A. Perez-Pinzon
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (volume 737)

Abstract

Cerebral ischemia causes cerebral blood flow (CBF) derangements resulting in neuronal damage by enhanced protein kinase C delta (δPKC) levels leading to hippocampal and cortical neuronal death after ischemia. Contrarily, activation of εPKC mediates ischemic tolerance by decreasing vascular tone providing neuroprotection. However, whether part of this protection is due to the role of differential isozymes of PKCs on CBF following cerebral ischemia remains poorly understood. Rats pretreated with a δPKC specific inhibitor (δV1-1, 0.5 mg/kg) exhibited attenuation of hyperemia and latent hypoperfusion characterized by vasoconstriction followed by vasodilation of microvessels after two-vessel occlusion plus hypotension. In an asphyxial cardiac arrest (ACA) model, rats treated with δV1-1 (pre- and postischemia) exhibited improved perfusion after 24 h and less hippocampal CA1 and cortical neuronal death 7 days after ACA. On the contrary, εPKC-selective peptide activator, conferred neuroprotection in the CA1 region of the rat hippocampus 30 min before induction of global cerebral ischemia and decreased regional CBF during the reperfusion phase. These opposing effects of δv. εPKC suggest a possible therapeutic potential by modulating CBF preventing neuronal damage after cerebral ischemia.

Keywords

Cerebral Blood Flow Cerebral Ischemia Global Cerebral Ischemia Normal Neuron Cerebral Blood Flow Change 
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 work was supported by National Institutes of Health grants NS45676-01, NS054147-01, NS34773, T32-NS007459-10, and American Heart Association-Philips grant 10POST4340011. Tat peptide, δV1-1, and ψεRACK were purchased from KAI Pharmaceuticals Inc., San Francisco, CA, USA.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Hung Wen Lin
    • 1
  • David Della-Morte
    • 1
  • John W. Thompson
    • 1
  • Victoria L. Gresia
    • 1
  • Srinivasan V. Narayanan
    • 1
  • R. Anthony DeFazio
    • 1
  • Ami P. Raval
    • 1
  • Isabel Saul
    • 1
  • Kunjan R. Dave
    • 1
  • Kahlilia C. Morris
    • 1
  • Min-Liang Si
    • 2
  • Miguel A. Perez-Pinzon
    • 1
  1. 1.Department of Neurology, Cerebral Vascular Disease Research CenterD4-5 University of Miami, Miller School of MedicineMiamiUSA
  2. 2.Department of PharmacologySouthern Illinois University School of MedicineSpringfieldUSA

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