Neuroprotection by Ozanimod Following Intracerebral Hemorrhage in Mice

Fei Wang; Xiangyu Zhang; Yang Liu; Zhe Li; Ruixue Wei; Yan Zhang; Ruiyi Zhang; Suliman Khan; V Wee Yong; Mengzhou Xue

doi:10.3389/fnmol.2022.927150

Neuroprotection by Ozanimod Following Intracerebral Hemorrhage in Mice

Front Mol Neurosci. 2022 Jun 15:15:927150. doi: 10.3389/fnmol.2022.927150. eCollection 2022.

Authors

Fei Wang^{1

2}, Xiangyu Zhang^{1

2}, Yang Liu^{1

2}, Zhe Li^{1

2}, Ruixue Wei^{1

2}, Yan Zhang^{1

2}, Ruiyi Zhang^{1

2}, Suliman Khan^{1

2}, V Wee Yong³, Mengzhou Xue^{1

2}

Affiliations

¹ Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
² Academy of Medical Science, Zhengzhou University, Zhengzhou, China.
³ Department of Clinical Neurosciences, The Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.

Abstract

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.

Keywords: Ozanimod; blood-brain barrier; brain edema; intracerebral hemorrhage; neuroprotection.