Effect of protein kinase C modulation on outcome of experimental CNS ischemia

Ken P. Madden, Wayne Clark, Abha Kochhar, Justin A. Zivin

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Protein kinase C (PKC) is an important intracellular regulator, and its activity may play a central role in the modulation of neuronal ischemic damage. Staurosporine and the compound H-7 are potent in vitro inhibitors of PKC, and 1,2-oleoylacetylglycerol (OAG) is an effective activator. We administered these compounds through a spinal subarachnoid catheter and demonstrated in vivo alteration of spinal cord PKC activity. We then tested the effects of altering PKC activity in a well-established rabbit model of reversible spinal cord ischemia. Animals within each experimental group were subjected to a range of spinal cord ischemic durations by temporary occlusion of the infrarenal abdominal aorta. Compared to control, both staurosporine and H-7 significantly shortened the duration of ischemia that the animals could tolerate, without developing permanent paraplegia. OAG resulted in an insignificant lengthening of the ischemic duration that the animals could withstand. The worsening of ischemic outcome by PKC inhibitors suggests that the enzyme is important for maintaining neurologic function under ischemic conditions, possibly secondary to modulation of intracellular calcium levels.

Original languageEnglish (US)
Pages (from-to)193-198
Number of pages6
JournalBrain Research
Volume547
Issue number2
DOIs
StatePublished - May 3 1991
Externally publishedYes

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Keywords

  • 1,2-Oleoylacetylglycerol (OAG)
  • Calcium
  • Compound H-7
  • Protein kinase C
  • Spinal ischemia
  • Staurosporine

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

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