Neuroinflammation Research Center (L.L., L.C.S., B.H., S.S., A.L., C.Z., M.Y., A.C.C., R.M.R.), Lerner Research Institute, Cleveland Clinic; Cleveland Clinic Lerner College of Medicine of Case Western Reserve University (B.P.); and Case Western Reserve University School of Medicine (B.B.), Cleveland, OH.
Neurol Neuroimmunol Neuroinflamm. 2015 Nov 19;2(6):e174. doi: 10.1212/NXI.0000000000000174. eCollection 2015 Dec.
Residual CXCR2 expression on CNS cells in Cxcr2 (+/-) →Cxcr2 (-/-) chimeric animals slowed remyelination after both experimental autoimmune encephalomyelitis and cuprizone-induced demyelination.
We generated Cxcr2 (fl/-) :PLPCre-ER(T) mice enabling an inducible, conditional deletion of Cxcr2 on oligodendrocyte lineage cells of the CNS. Cxcr2 (fl/-) :PLPCre-ER(T) mice were evaluated in 2 demyelination/remyelination models: cuprizone-feeding and in vitro lysophosphatidylcholine (LPC) treatment of cerebellar slice cultures.
Cxcr2 (fl/-) :PLPCre-ER(T)(+) (termed Cxcr2-cKO) mice showed better myelin repair 4 days after LPC-induced demyelination of cerebellar slice cultures. Cxcr2-cKOs also displayed enhanced hippocampal remyelination after a 2-week recovery from 6-week cuprizone feeding.
Using 2 independent demyelination/remyelination models, our data document enhanced myelin repair in Cxcr2-cKO mice, consistent with the data obtained from radiation chimerism studies of germline CXCR2. Further experiments are appropriate to explore how CXCR2 function in the oligodendrocyte lineage accelerates myelin repair.
在 Cxcr2(+/-)→Cxcr2(-/-)嵌合体动物中，CNS 细胞上残余的 CXCR2 表达减缓了实验性自身免疫性脑脊髓炎和杯状醇诱导的脱髓鞘后的再髓鞘化。
我们生成了 Cxcr2(fl/-):PLPCre-ER(T) 小鼠，使中枢神经系统的少突胶质细胞谱系细胞上的 Cxcr2 能够进行诱导性、条件性缺失。在 2 种脱髓鞘/再髓鞘模型中评估了 Cxcr2(fl/-):PLPCre-ER(T) 小鼠：杯状醇喂养和体外溶血磷脂酰胆碱 (LPC) 处理小脑切片培养物。
在 LPC 诱导的小脑切片培养物脱髓鞘后 4 天，Cxcr2(fl/-):PLPCre-ER(T)(+)（称为 Cxcr2-cKO）小鼠显示出更好的髓鞘修复。在经过 6 周杯状醇喂养后 2 周恢复期间，Cxcr2-cKO 还显示出增强的海马再髓鞘化。
使用 2 种独立的脱髓鞘/再髓鞘模型，我们的数据记录了 Cxcr2-cKO 小鼠中髓鞘修复的增强，与源自生殖系 CXCR2 的辐射嵌合体研究中获得的数据一致。进一步的实验适合探索 CXCR2 在少突胶质细胞谱系中的功能如何加速髓鞘修复。
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