Wang Fei, Zhang Xiangyu, Liu Yang, Li Zhe, Wei Ruixue, Zhang Yan, Zhang Ruiyi, Khan Suliman, Yong V Wee, Xue Mengzhou
Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Academy of Medical Science, Zhengzhou University, Zhengzhou, China.
Front Mol Neurosci. 2022 Jun 15;15:927150. doi: 10.3389/fnmol.2022.927150. eCollection 2022.
The destruction of the blood-brain barrier (BBB) after intracerebral hemorrhage (ICH) is associated with poor prognosis. Modulation of sphingosine 1-phosphate receptor (S1PR) may improve outcomes from ICH. Ozanimod (RPC-1063) is a newly developed S1PR regulator which can selectively modulate type 1/5 sphingosine receptors. Here, we studied the impact of Ozanimod on neuroprotection in an experimental mouse model of ICH, induced by injecting collagenase type VII into the basal ganglia. Ozanimod was administered by gavage 2 h after surgery and once a day thereafter until sacrifice. The results demonstrate that Ozanimod treatment improved neurobehavioral deficits in mice and decreased weight loss after ICH. Ozanimod significantly reduced the density of activated microglia and infiltrated neutrophils in the perihematoma region. Furthermore, Ozanimod reduced hematoma volume and water content of the ICH brain. The results of TUNEL staining indicate that Ozanimod mitigated brain cell death. The quantitative data of Evans blue (EB) staining showed that Ozanimod reduced EB dye leakage. Overall, Ozanimod reduces the destruction of the BBB and exert neuroprotective roles following ICH in mice.
脑出血（ICH）后血脑屏障（BBB）的破坏与预后不良相关。调节1-磷酸鞘氨醇受体（S1PR）可能改善ICH的预后。奥扎莫德（RPC-1063）是一种新开发的S1PR调节剂，可选择性调节1/5型鞘氨醇受体。在此，我们研究了奥扎莫德对通过向基底神经节注射VII型胶原酶诱导的ICH实验小鼠模型中神经保护的影响。奥扎莫德在手术后2小时通过灌胃给药，此后每天给药一次，直至处死。结果表明，奥扎莫德治疗改善了小鼠的神经行为缺陷，并减少了ICH后的体重减轻。奥扎莫德显著降低了血肿周围区域活化小胶质细胞和浸润中性粒细胞的密度。此外，奥扎莫德减少了ICH脑的血肿体积和含水量。TUNEL染色结果表明奥扎莫德减轻了脑细胞死亡。伊文思蓝（EB）染色的定量数据显示奥扎莫德减少了EB染料渗漏。总体而言，奥扎莫德减少了BBB的破坏，并在小鼠ICH后发挥神经保护作用。
