Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
Exp Neurol. 2013 Nov;249:33-8. doi: 10.1016/j.expneurol.2013.08.005. Epub 2013 Aug 16.
Normobaric oxygen (NBO) reduces infarction at 24-48 h in experimental models of focal cerebral ischemia. However, to be clinically relevant, longer term safety and efficacy must be explored. Here, we assessed the effects of NBO on glial activation, neurovascular recovery, and behavioral outcomes at 2 weeks after transient focal ischemia in rats. 100 min transient focal ischemia was induced by intraluminal occlusion of the middle cerebral artery in adult male Sprague-Dawley rats. Animals were randomized into sham, controls or 85'NBO started 15 min after ischemic onset. Infarct volumes and behavioral outcomes were blindly quantified. Immunohistochemistry was used to examine the effects of NBO on glial activation and neurovascular responses. After 2 weeks of reperfusion the infarct volume was marked reduced in animals subjected to NBO. They also had better outcomes in forelimb placement test and in body-swing test and weight loss reduction. After 14 days, NBO decreased expression of Iba1, a marker of activated microglia, and GFAP, a marker of activated astrocytes. NBO treatment had no detectable effect on angiogenesis. These results suggest that protective effects of NBO may persist for up to 2 weeks post-stroke.
常压氧(NBO)可减少实验性局灶性脑缺血模型中 24-48 小时的梗死。然而,为了具有临床相关性,必须探索更长时间的安全性和有效性。在这里,我们评估了 NBO 对大鼠短暂性局灶性缺血后 2 周时神经胶质激活、神经血管恢复和行为结果的影响。通过大脑中动脉腔内闭塞在成年雄性 Sprague-Dawley 大鼠中诱导 100 分钟的短暂性局灶性缺血。动物随机分为假手术组、对照组或缺血后 15 分钟开始的 85'NBO 组。盲法量化梗死体积和行为结果。免疫组织化学用于检查 NBO 对神经胶质激活和神经血管反应的影响。再灌注 2 周后,NBO 组动物的梗死体积明显减少。它们在前肢放置试验和身体摆动试验以及体重减轻方面也有更好的结果。14 天后,NBO 降低了小胶质细胞活化标志物 Iba1 和星形胶质细胞活化标志物 GFAP 的表达。NBO 治疗对血管生成没有明显影响。这些结果表明,NBO 的保护作用可能持续到中风后 2 周。