Inhibition of 12/15-lipoxygenase as therapeutic strategy to treat stroke Academic Article uri icon

Overview

MeSH Major

  • Arachidonate 12-Lipoxygenase
  • Arachidonate 15-Lipoxygenase
  • Lipoxygenase Inhibitors
  • Stroke

abstract

  • Targeting newly identified damage pathways in the ischemic brain can help to circumvent the currently severe limitations of acute stroke therapy. Here we show that the activity of 12/15-lipoxygenase was increased in the ischemic mouse brain, and 12/15-lipoxygenase colocalized with a marker for oxidized lipids, MDA2. This colocalization was also detected in the brain of 2 human stroke patients, where it also coincided with increased apoptosis-inducing factor. A novel inhibitor of 12/15-lipoxygenase, LOXBlock-1, protected neuronal HT22 cells against oxidative stress. In a mouse model of transient focal ischemia, the inhibitor reduced infarct sizes both 24 hours and 14 days poststroke, with improved behavioral parameters. Even when treatment was delayed until at least 4 hours after onset of ischemia, LOXBlock-1 was protective. Furthermore, it reduced tissue plasminogen activator-associated hemorrhage in a clot model of ischemia/reperfusion. This study establishes inhibition of 12/15-lipoxygenase as a viable strategy for first-line stroke treatment.

publication date

  • January 2013

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3563836

Digital Object Identifier (DOI)

  • 10.1002/ana.23734

PubMed ID

  • 23192915

Additional Document Info

start page

  • 129

end page

  • 35

volume

  • 73

number

  • 1