Spatio-temporal properties of 5-lipoxygenase expression and activation in the brain after focal cerebral ischemia in rats

Life Sci. 2006 Sep 20;79(17):1645-56. doi: 10.1016/j.lfs.2006.05.022. Epub 2006 Jun 2.

Abstract

The role of 5-lipoxygenase (5-LOX) in brain injury after cerebral ischemia has been reported; however, the spatio-temporal properties of 5-LOX expression and the enzymatic activation are unclear. To determine these properties, we observed post-ischemic 5-LOX changes from 3 h to 14 days after reperfusion in rats with transient focal cerebral ischemia induced by 30 min of middle cerebral artery occlusion. We found that the expression of 5-LOX, both mRNA and protein, was increased in the ischemic core 12-24 h after reperfusion, and in the boundary zone adjacent to the ischemic core 7-14 days after reperfusion. The increased 5-LOX was primarily localized in the neurons in the ischemic core at 24 h, but in the proliferated astrocytes in the boundary zone 14 days after reperfusion. As 5-LOX metabolites, the level of cysteinyl-leukotrienes in the ischemic brain was substantially increased 3 h to 24 h, near control at 3 days, and moderately increased again 7 days after reperfusion; whereas the level of LTB(4) was increased mildly 3 h but substantially 7-14 days after reperfusion. Thus, we conclude that 5-LOX expression and the enzymatic activity are increased after focal cerebral ischemia, and spatio-temporally involved in neuron injury in the acute phase and astrocyte proliferation in the late phase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Arachidonate 5-Lipoxygenase / biosynthesis*
  • Arachidonate 5-Lipoxygenase / genetics
  • Arterial Occlusive Diseases / metabolism
  • Astrocytes / enzymology
  • Astrocytes / pathology
  • Brain / enzymology*
  • Brain / pathology
  • Cell Proliferation
  • Chronic Disease
  • Disease Models, Animal
  • Enzyme Activation
  • Gene Expression
  • Immunoenzyme Techniques
  • Ischemic Attack, Transient / enzymology*
  • Ischemic Attack, Transient / pathology
  • Leukotrienes / metabolism
  • Male
  • Neurons / enzymology
  • Neurons / pathology
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / enzymology*
  • Reperfusion Injury / pathology
  • Time Factors

Substances

  • Leukotrienes
  • RNA, Messenger
  • Arachidonate 5-Lipoxygenase