Administration of the p38 MAPK inhibitor SB203580 affords brain protection with a wide therapeutic window against focal ischemic insult

Chun Shu Piao, Jung Bin Kim, Pyung Lim Han, Ja Kyeong Lee*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

119 Scopus citations

Abstract

We have reported previously the delayed and differential induction of p38α and p38β mitogen-activated protein kinases (MAPKs) in microglia and astrocytes, respectively, in brain after transient global ischemia. We report here the sustained induction and activation of p38α MAPK in activating microglia in rat brain after transient middle cerebral artery occlusion (MCAO). The intraventricular administration of SB203580, a p38 MAPK inhibitor, 30 min before MCAO reduced the infarct volume to 50% of the control, which was accompanied by the significant improvement of neurological deficits. More interestingly, the infarct volume was reduced to 72% and 77% when SB203580 was administered 6 hr and 12 hr after MCAO, respectively. The induction of various factors involved in inflammatory processes, such as inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and cyclooxygenase-2 (COX-2), was suppressed by the administration of SB203580 at 6 hr after MCAO. These results suggest that sustained activation of p38 MAPK pathway and p38 MAPK-associated inflammatory processes play a crucial role in postischemic brain.

Original languageEnglish (US)
Pages (from-to)537-544
Number of pages8
JournalJournal of Neuroscience Research
Volume73
Issue number4
DOIs
StatePublished - Aug 15 2003

Keywords

  • MCAO
  • Microglia
  • Neuroprotection
  • p38 MAPK
  • SB203580

ASJC Scopus subject areas

  • Neuroscience(all)

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