Arachidonic acid and leukotriene C4: role in transient cerebral ischemia of gerbils.
Accumulation of arachidonic acid (AA) is greatest in brain regions most sensitive to transient ischemia. Free AA released after ischemia is either: 1) reincorporated into the membrane phospholipids, or 2) oxidized during reperfusion by lipoxygenases and cyclooxygenases, producing leukotrienes (LT), prostaglandins, thromboxanes and oxygen radicals. AA, its metabolite LTC4 and lipid peroxides (generated during AA metabolism) have been implicated in the blood-brain barrier (BBB) dysfunction, edema and neuronal death after ischemia/reperfusion. This report describes the time course of AA release, LTC4 accumulation and association with the physiological outcome during transient cerebral ischemia of gerbils. Significant amount of AA was detected immediately after 10 min ischemia (0 min reperfusion) which returned to sham levels within 30 min reperfusion. A later release of AA occurred after 1 d. LTC4 levels were elevated at 0-6 h and 1 d after ischemia. Increased lipid peroxidation due to AA metabolism was observed between 2-6 h. BBB dysfunction occurred at 6 h. Significant edema developed at 1 and 2 d after ischemia and reached maximum at 3 d. Ischemia resulted in approximately 80% neuronal death in the CA1 hippocampal region. Pretreatment with a 5-lipoxygenase inhibitor, AA861 resulted in significant attenuation of LTC4 levels (Baskaya et al. 1996. J. Neurosurg. 85: 112-116) and CA1 neuronal death. Accumulation of AA and LTC4, together with highly reactive oxygen radicals and lipid peroxides, may alter membrane permeability, resulting in BBB dysfunction, edema and ultimately to neuronal death.
Rao
A M
AM
Department of Neurological Surgery, University of Wisconsin, Madison 53792-3232, USA. adibhatl@neurosurg.wisc.edu
Hatcher
J F
JF
Kindy
M S
MS
Dempsey
R J
RJ
D000818:Animals; D016718:Arachidonic Acid / Q000502:physiology*; D001812:Blood-Brain Barrier; D001929:Brain Edema / Q000378:metabolism / Q000473:pathology; D005849:Gerbillinae; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D017997:Leukotriene C4 / Q000502:physiology*; D015227:Lipid Peroxidation; D008297:Male
D016718:Arachidonic Acid; D017997:Leukotriene C4