Division of Neurosurgical Research, Medical Faculty Mannheim, University of Heidelberg, Germany.
Exp Neurol. 2012 Sep;237(1):18-25. doi: 10.1016/j.expneurol.2012.06.007. Epub 2012 Jun 21.
Tissue hypoxia may play an important role in the development of ischemic brain damage. In the present study we investigated in a rat model of transient focal brain ischemia the neuroprotective effects of increasing the blood oxygen transport capacity by applying a semifluorinated alkane (SFA)-containing emulsion together with normobaric hyperoxygenation (NBO). The spread of tissue hypoxia was studied using pimonidazole given prior to filament-induced middle cerebral artery occlusion (MCAO, 2 h). Treatment consisted of intravenous injection of saline or the SFA-containing emulsion (0.5 or 1.0 ml/100g body weight; [SFA(0.5) or SFA(1.0)]) either upon establishing MCAO (early treatment) or after filament removal (delayed treatment). After injection NBO was administered for 8 h (early treatment) or 6 h (delayed treatment). Experiments were terminated 8 or 24 h after MCAO. In serial brain sections tissue hypoxia and irreversible cell damage were quantitatively determined. Furthermore, we studied hypoxia-related gene expression (VEGF, flt-1). Early treatment significantly (p<0.05) reduced the volumes of tissue damage (8 h after MCAO: SFA(1.0), 57±34 mm³; controls, 217±70 mm³; 24 h after MCAO: SFA(1.0), 189±82 mm³; controls, 317±60 mm³) and of P-Add immunoreactivity (8 h after MCAO: SFA(1.0), 261±37 mm³; controls, 339±26 mm³; 24h after MCAO: SFA(1.0), 274±47 mm³; controls, 364±46 mm³). Delayed treatment was comparably successful. The volume of the hypoxic penumbra was not decreased by the treatment. Similarly, VEGF and flt-1 mRNA levels did not differ between the experimental groups. From these data we conclude that increasing the blood oxygen transport capacity in the plasma compartment provides a neuroprotective effect by alleviating the severity of hypoxia to a level sufficient to prevent cells from transition into irreversible damage.
组织缺氧可能在缺血性脑损伤的发展中发挥重要作用。在本研究中，我们在大鼠短暂性局灶性脑缺血模型中研究了通过应用含有半氟化烷烃（SFA）的乳液并进行常压高氧（NBO）来增加血液氧运输能力的神经保护作用。使用匹莫硝唑在栓子诱导的大脑中动脉闭塞（MCAO，2 h）之前给药来研究组织缺氧的扩散。治疗包括在建立 MCAO 时（早期治疗）或在栓子去除后（延迟治疗）静脉注射生理盐水或含有 SFA 的乳液（0.5 或 1.0 ml/100g 体重；[SFA（0.5）或 SFA（1.0）]）。注射后进行 8 小时（早期治疗）或 6 小时（延迟治疗）的 NBO 治疗。MCAO 后 8 或 24 小时终止实验。在连续脑切片中定量测定组织缺氧和不可逆细胞损伤。此外，我们研究了与缺氧相关的基因表达（VEGF，flt-1）。早期治疗可显著（p<0.05）减少组织损伤体积（MCAO 后 8 h：SFA（1.0），57±34mm³；对照组，217±70mm³；MCAO 后 24 h：SFA（1.0），189±82mm³；对照组，317±60mm³）和 P-Add 免疫反应性（MCAO 后 8 h：SFA（1.0），261±37mm³；对照组，339±26mm³；MCAO 后 24 h：SFA（1.0），274±47mm³；对照组，364±46mm³）。延迟治疗同样成功。治疗并未减少缺氧半影区的体积。同样，实验组之间的 VEGF 和 flt-1 mRNA 水平没有差异。从这些数据我们得出结论，增加血浆中血液氧运输能力通过缓解缺氧程度到足以防止细胞不可逆损伤的水平，提供神经保护作用。
