Modifying neurorepair and neuroregenerative factors with tPA and edaravone after transient middle cerebral artery occlusion in rat brain

Kentaro Deguchi, Kazunori Miyazaki, Fengfeng Tian, Ning Liu, Wentao Liu, Hiromi Kawai, Yosiho Omote, Syoichiro Kono, Taijun Yunoki, Shoko Deguchi, Koji Abe

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Changes in expression of neurorepair and neuroregenerative factors were examined after transient cerebral ischemia in relation to the effects of tissue plasminogen activator (tPA) and the free radical scavenger edaravone. Physiological saline or edaravone was injected twice during 90 min of transient middle cerebral artery occlusion (tMCAO) in rats, followed by the same saline or tPA at reperfusion. Sizes of the infarct and protein factors relating to neurorepair and neuroregeneration were examined at 4 d after tMCAO. The protein factors examined were: a chondroitin sulfate proteoglycan neurocan, semaphorin type 3A (Sema3A), a myelin-associated glycoprotein receptor (Nogo receptor, Nogo-R), a synaptic regenerative factor (growth associated protein-43, GAP43), and a chemotropic factor netrin receptor (deleted in colorectal cancer, DCC). Two groups treated by edaravone only or edaravone plus tPA showed a reduction in infarct volume compared to the two groups treated by vehicle only or vehicle plus tPA. Immunohistochemistry and western blot analyses indicated that protein expression of neurocan, Sema3A, Nogo-R, GAP43, and DCC was decreased with tPA, but recovered with edaravone. Additive edaravone prevented the reductions of these five proteins induced by tPA. The present study demonstrates for the first time that exogenous tPA reduced protein factors involved in inhibiting and promoting axonal growth, but that edaravone ameliorated such damage in brain repair after acute ischemia.

Original languageEnglish
Pages (from-to)168-177
Number of pages10
JournalBrain Research
Volume1436
DOIs
Publication statusPublished - Feb 3 2012

Keywords

  • Acute ischemia
  • Axonal growth
  • Edaravone
  • Neuroregeneration
  • Neurorepair
  • Tissue plasminogen activator

ASJC Scopus subject areas

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

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