Inhibition of 12/15-Lipoxygenase as Therapeutic Strategy to Treat Stroke

Yigitkanli K., Pekcec A., Karatas H., Pallast S., Mandeville E., Joshi N., ...More

ANNALS OF NEUROLOGY, vol.73, no.1, pp.129-135, 2013 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 73 Issue: 1
  • Publication Date: 2013
  • Doi Number: 10.1002/ana.23734
  • Title of Journal : ANNALS OF NEUROLOGY
  • Page Numbers: pp.129-135


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. ANN NEUROL 2013;73:129-135