Baskaya M K, Hu Y, Donaldson D, Maley M, Rao A M, Prasad M R, Dempsey R J
Department of Neurological Surgery, University of Wisconsin Clinical Science Center, Madison, USA.
J Neurosurg. 1996 Jul;85(1):112-6. doi: 10.3171/jns.1996.85.1.0112.
This study examined the effect of AA-861, a specific 5-lipoxygenase inhibitor, on brain levels of leukotriene C4 (LTC4) and correlated any changes with changes in edema formation and cerebral blood flow (CBF) after transient ischemia in gerbils. Brain levels of LTC4 were observed to be increased at 1, 2, and 6 hours of reperfusion following 20 minutes of occlusion. At 2 hours of reperfusion, a pretreatment dose of 1000 mg/kg of AA-861 was required to inhibit more than 90% of the reperfusion-induced increases in brain LTC4. At this dose, inhibition of LTC4 production was observed at 2 and 6 hours of reperfusion. The specific gravity of both the cortex and subcortex was decreased at 6 hours of reperfusion after 20 minutes of occlusion. At 2 hours of reperfusion, no significant difference was observed in the specific gravity of the cortex and subcortex regions of gerbils pretreated with AA-861 or with vehicle, but at 6 hours of reperfusion significant positive differences were observed. Cerebral blood flow decreased to approximately 10% of preocclusion values during occlusion and returned to near-preocclusion values after 10 minutes of reperfusion. No significant differences were observed in regional CBF in the AA-861- and vehicle-pretreated gerbils during reperfusion. These findings indicate that LTC4 production after transient cerebral ischemia may be an important contributor to the development of cerebral edema and that CBF does not mediate the LTC4-involved development of edema.
本研究检测了特异性5-脂氧合酶抑制剂AA-861对沙土鼠短暂性脑缺血后白三烯C4（LTC4）脑内水平的影响，并将其任何变化与水肿形成及脑血流量（CBF）的变化相关联。在阻断20分钟后的再灌注1小时、2小时和6小时，观察到脑内LTC4水平升高。在再灌注2小时时，需要1000mg/kg的AA-861预处理剂量才能抑制超过90%的再灌注诱导的脑LTC4升高。在此剂量下，在再灌注2小时和6小时观察到LTC4生成受到抑制。在阻断20分钟后的再灌注6小时，皮质和皮质下的比重均降低。在再灌注2小时时，用AA-861或赋形剂预处理的沙土鼠皮质和皮质下区域的比重未观察到显著差异，但在再灌注6小时时观察到显著的正差异。在阻断期间，脑血流量降至阻断前值的约10%，再灌注10分钟后恢复至接近阻断前值。在再灌注期间，在AA-861和赋形剂预处理的沙土鼠中，区域脑血流量未观察到显著差异。这些发现表明，短暂性脑缺血后LTC4的产生可能是脑水肿发展的一个重要因素，并且脑血流量不介导涉及LTC4的水肿发展。
