Veltkamp Roland, Bieber Katja, Wagner Simone, Beynon Christopher, Siebing Dirk A, Veltkamp Claudia, Schwaninger Markus, Marti Hugo H
Department of Neurology, Ruprecht-Karls-University Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
Brain Res. 2006 Mar 3;1076(1):231-7. doi: 10.1016/j.brainres.2006.01.013. Epub 2006 Feb 9.
Hyperbaric oxygen (HBO) has been shown to preserve the integrity of the blood-brain barrier after cerebral ischemia. However, the underlying molecular mechanisms are currently unknown. We examined the effect of HBO on postischemic expression of the basal laminar component laminin-5 and on plasma matrix metalloproteinase-9 (MMP) levels. Wistar rats underwent occlusion of the middle cerebral artery (MCAO) for 2 h. With a delay of 45 min after filament introduction, animals breathed either 100% O2 at 1.0 atmosphere absolute (ata; NBO) or at 3.0 ata (HBO) for 1 h in an HBO chamber. Laminin-5 expression was quantified on immunohistochemical sections after 24 h of reperfusion. Plasma MMP-9 levels were measured using gelatin zymography before MCAO as well as 0, 6 and 24 h after reperfusion. Immunohistochemistry 24 h after ischemia revealed a decrease of vascular laminin-5 staining in the ischemic striatum to 43 +/- 26% of the contralateral hemisphere in the NBO group which was significantly attenuated to 73 +/- 31% in the HBO group. Densitometric analysis of zymography bands yielded significantly larger plasma MMP-9 levels in the NBO group compared to the HBO group 24 h after ischemia. In conclusion, HBO therapy attenuates ischemic degradation of cerebral microvascular laminin-5 and blocks postischemic plasma MMP-9 upregulation.
高压氧(HBO)已被证明可在脑缺血后维持血脑屏障的完整性。然而,其潜在的分子机制目前尚不清楚。我们研究了HBO对缺血后基底膜成分层粘连蛋白-5表达以及血浆基质金属蛋白酶-9(MMP)水平的影响。Wistar大鼠大脑中动脉闭塞(MCAO)2小时。在插入线栓后延迟45分钟,动物在HBO舱内分别于1.0绝对大气压(ata;常压氧,NBO)或3.0 ata(HBO)下呼吸100%氧气1小时。再灌注24小时后,对免疫组织化学切片上的层粘连蛋白-5表达进行定量分析。在MCAO前以及再灌注后0、6和24小时,使用明胶酶谱法测量血浆MMP-9水平。缺血24小时后的免疫组织化学显示,NBO组缺血纹状体中血管层粘连蛋白-5染色减少至对侧半球的43±26%,而HBO组显著减轻至73±31%。酶谱带的光密度分析显示,缺血24小时后,NBO组的血浆MMP-9水平显著高于HBO组。总之,HBO治疗可减轻脑微血管层粘连蛋白-5的缺血性降解,并阻止缺血后血浆MMP-9的上调。