Inhibition of Neutrophil Migration by a Protein Kinase Inhibitor for the Treatment of Ischemic Brain Infarction

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Author(s)

Abstract

This study investigated the therapeutic potential of agents that inhibited neutrophil infiltration in cerebral ischemic infarction. The migration of neutrophils elicited by <I>N</I>-formyl-methionyl-leucyl-phenylalanine, tumor necrosis factor, C5a or platelet-activating factor was potently inhibited by fasudil, an inhibitor of protein kinases including rho kinase, protein kinase C and myosin light chain kinase, and hydroxy fasudil, a metabolite of fasudil, in vitro. In a microembolism model in rats, myeloperoxidase-quantified neutrophil accumulation in the ischemic brain was observed 24 hr after embolization. Intravenous administration of fasudil prevented the accumulation of neutrophils. In rats given fasudil, myeloperoxidase activity in the ipsilateral hemisphere (0.04±0.01 unit/g wet tissue) was significantly lower than that in ischemic rats (0.11±0.02 unit/g wet tissue). Fasudil also significantly reduced the size of the infarct area and improved neurological functions. These results suggest that neutrophil infiltration into the ischemic brain is involved in the pathogenesis of ischemic injury and that inhibiting neutrophil infiltration may provide an effective therapeutic intervention to reduce ischemic injury.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 80(1), 41-48, 1999-05-01

    The Japanese Pharmacological Society

References:  37

Cited by:  12

Codes

  • NII Article ID (NAID)
    10008194551
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    4733048
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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