Schäbitz Wolf-Ruediger, Schade Holger, Heiland Sabine, Kollmar Rainer, Bardutzky Jürgen, Henninger Nils, Müller Harald, Carl Ulrich, Toyokuni Shinya, Sommer Clemens, Schwab Stefan
Department of Neurology , University of Heidelberg, Germany.
Stroke. 2004 May;35(5):1175-9. doi: 10.1161/01.STR.0000125868.86298.8e. Epub 2004 Apr 1.
Hyperbaric oxygenation (HBO) after focal cerebral ischemia reduces infarct size and improves outcome when applied early after stroke. Here, we evaluated effects of HBO on permanent focal cerebral ischemia and applied magnetic resonance imaging (MRI) monitoring to study lesion evolution.
Rats underwent permanent middle cerebral artery occlusion (MCAO). Two hours later, animals were treated with HBO (100% O(2)/2 atm; n=17) for 1 hour or treated with room air (n=17). Animals underwent serial MRI studies (DWI, PI, T2) beginning 90 minutes after MCAO. Neuroscore was assessed (5-point rating scale). Animals were euthanized and brains were 2,3,5-triphenyltetrazolium chloride (TTC)-stained for infarct volume calculation 120 hours after MCAO. Immunohistochemistry was performed with antibodies against c-FOS and 4-hydroxy-2-nonenal-modified proteins (HNE) to check for effects of oxidative stress caused by HBO treatment.
HBO reduced infarct volume by 38% (P<0.001). As shown by MRI, neuroprotection began 5 hours after ischemia and remained effective for 5 days. The relative regional cerebral blood flow was not different between groups at 3.5 and 5 hours after occlusion. There was less neurological deficit in HBO-treated animals compared with controls (P<0.05). Lipid peroxidation of cerebral vessels after HBO treatment as measured by HNE staining and pattern of c-FOS induction were not significantly different between groups at 3.5 and 8 hours after ischemia.
As monitored by MRI HBO treatment reversed ischemic lesion size between 3 and 5 hours after ischemia and achieved a long-lasting neuroprotective effect without significant oxidative damage.
局灶性脑缺血后早期应用高压氧（HBO）可减小梗死灶大小并改善预后。在此，我们评估了HBO对永久性局灶性脑缺血的影响，并应用磁共振成像（MRI）监测来研究损伤演变。
大鼠接受永久性大脑中动脉闭塞（MCAO）。两小时后，动物接受1小时的HBO治疗（100% O₂/2个大气压；n = 17）或接受室内空气治疗（n = 17）。在MCAO后90分钟开始对动物进行系列MRI研究（弥散加权成像、灌注成像、T2加权成像）。评估神经评分（5分制量表）。在MCAO后120小时对动物实施安乐死，并对大脑进行2,3,5-三苯基氯化四氮唑（TTC）染色以计算梗死体积。用抗c-FOS和4-羟基-2-壬烯醛修饰蛋白（HNE）的抗体进行免疫组织化学检测，以检查HBO治疗引起的氧化应激效应。
HBO使梗死体积减小了38%（P < 0.001）。如MRI所示，神经保护在缺血后5小时开始，并持续有效5天。闭塞后3.5小时和5小时，两组之间的相对局部脑血流量没有差异。与对照组相比，接受HBO治疗的动物神经功能缺损较少（P < 0.05）。缺血后3.5小时和8小时，通过HNE染色测量的HBO治疗后脑血管脂质过氧化和c-FOS诱导模式在两组之间没有显著差异。
通过MRI监测，HBO治疗在缺血后3至5小时逆转了缺血性损伤大小，并实现了持久的神经保护作用，而无明显的氧化损伤。
