Wang Tao, He Mindi, Zha Xiang-Ming
Department of Physiology and Cell Biology, University of South Alabama College of Medicine, Mobile, AL, USA.
Brain Hemorrhages. 2020 Dec;1(4):185-191. doi: 10.1016/j.hest.2020.10.001. Epub 2020 Oct 21.
Hemorrhagic transformation (HT) following ischemia is one complication which worsens stroke outcome. During and after ischemia-reperfusion, persistent reduction of brain pH occurs. In a recent study, we found that GPR68 functions as a neuronal proton receptor and mediates a protective pathway in brain ischemia. Here, we asked whether GPR68 contributes HT after ischemia. At 24 hr after transient middle cerebral artery occlusion (tMCAO), 58% of the wild-type (WT) mice exhibited some degrees of mild HT. At 72 hr, 95% of the WT showed HT with 42% exhibited large "parenchymal" type hemorrhage. In the GPR68-/- mice, there was a trend of increase in both the incidence and severity of HT at both time points. Mice with severe hemorrhage exhibited significantly larger infarct than those with no to mild hemorrhage. Next, we compared % infarct of GPR68-/- vs WT based on their HT categories. GPR68 deletion increased % infarct when the HT severity is mild. In contrast, for mice exhibiting large area HT, the two genotypes had no difference in % infarct. These data showed that GPR68-dependent signaling leads to protection when HT is mild.
缺血后出血性转化（HT）是一种会使中风预后恶化的并发症。在缺血再灌注期间及之后，脑内pH值会持续降低。在最近的一项研究中，我们发现GPR68作为一种神经元质子受体，在脑缺血中介导一条保护途径。在此，我们探究了GPR68是否在缺血后导致HT。在短暂性大脑中动脉闭塞（tMCAO）后24小时，58%的野生型（WT）小鼠出现了一定程度的轻度HT。在72小时时，95%的WT小鼠出现了HT，其中42%出现了大面积的“实质”型出血。在GPR68基因敲除（GPR68-/-）小鼠中，两个时间点的HT发生率和严重程度均有增加趋势。出现严重出血的小鼠梗死灶明显大于无出血至轻度出血的小鼠。接下来，我们根据HT类别比较了GPR68-/-小鼠与WT小鼠的梗死灶百分比。当HT严重程度为轻度时，GPR68基因缺失会增加梗死灶百分比。相反，对于出现大面积HT的小鼠，两种基因型的梗死灶百分比没有差异。这些数据表明，当HT为轻度时，GPR68依赖性信号传导具有保护作用。
