Pille Johannes A, Riess Matthias L
Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA;
Department of Anesthesiology, University Medicine Greifswald, 17475 Greifswald, Germany.
Brain Sci. 2021 Jan 18;11(1):122. doi: 10.3390/brainsci11010122.
Outcome after cerebral ischemia is often dismal. Reperfusion adds significantly to the ischemic injury itself. Therefore, new strategies targeting ischemia/reperfusion (I/R) injury are critically needed. Poloxamer (P)188, an amphiphilic triblock copolymer, is a highly promising pharmacological therapeutic as its capability to insert into injured cell membranes has been reported to protect against I/R injury in various models. Although mitochondrial function particularly profits from P188 treatment after I/R, it remains unclear if this beneficial effect occurs directly or indirectly. Here, rat isolated brain mitochondria underwent oxidative stress in vivo by asphyxial cardiac arrest or in vitro by the addition of hydrogen peroxide (HO) after isolation. Mitochondrial function was assessed by adenosine triphosphate synthesis, oxygen consumption, and calcium retention capacity. Both asphyxia and HO exposure significantly impaired mitochondrial function. P188 did not preserve mitochondrial function after either injury mechanism. Further research is indicated.
脑缺血后的预后通常很差。再灌注会显著加重缺血损伤本身。因此，迫切需要针对缺血/再灌注（I/R）损伤的新策略。泊洛沙姆（P）188是一种两亲性三嵌段共聚物，是一种非常有前景的药物治疗方法，因为据报道它能够插入受损细胞膜，在各种模型中预防I/R损伤。尽管线粒体功能在I/R后特别受益于P188治疗，但这种有益作用是直接还是间接发生仍不清楚。在这里，大鼠分离的脑线粒体在体内通过窒息性心脏骤停经历氧化应激，或在体外分离后通过添加过氧化氢（HO）经历氧化应激。通过三磷酸腺苷合成、氧气消耗和钙保留能力评估线粒体功能。窒息和HO暴露均显著损害线粒体功能。在任何一种损伤机制后，P188均不能保留线粒体功能。需要进一步研究。
