Regulation of myelination after spinal cord injury

本项目将研究脊髓损伤后少突胶质细胞祖细胞（OPCs）的调控 对小鼠OPCs在成年中枢神经系统中可以分化为髓鞘再生少突胶质细胞（OLs），但是在成年中枢神经系统中， 在成人中枢神经系统损伤的情况下，促进这种转化尚不清楚。大多数关于OPC功能的研究， 髓鞘形成使用化学脱髓鞘或新生细胞培养模型，其不模拟体内髓鞘形成。 成人脊髓挫伤的环境。因此，该项目与NIH的使命相关，因为它将 包括基础科学研究，以辨别自发OL再生和髓鞘修复的机制 SCI之后实验将使用临床相关的脊柱挫伤模型来评估机制 在SCI后调节OPC存活、增殖和分化成新的OL。如果没有髓磷脂， 用于传导动作电位的备用或再生轴突将受到严重阻碍或完全阻断。 我们将使用报告小鼠和Cre-Lox系统来抑制谷氨酸从轴突或特定的细胞内释放， 信号分子，以确定这些机制是否调节SCI后OPC功能。我们还将使用 一种新的模型，用于诱导SCI后脱髓鞘，以确定OPC修复是否以及何时最大或何时最大。 受损，因为我们新的飞行员数据表明，它可能会随着受伤后的时间而受损。如果成功，该项目将 提供了关于OPCs和髓鞘形成如何在成人受损神经系统中调节的新见解， 可能提供新的治疗靶点，通过增强轴突和神经元的功能， 髓鞘形成

This project will study how oligodendrocyte progenitor cells (OPCs) are regulated after spinal cord injury (SCI) in mice. OPCs can differentiate into remyelinating oligodendrocytes (OLs) in the adult CNS, but what signals promote this transformation are unclear in the setting of adult CNS trauma. Most studies of OPC function and myelination use chemical demyelination or neonatal cell culture models, which do not mimic the in vivo environment of the contused adult spinal cord. Thus, this project is relevant to the NIH mission since it will encompass basic science studies to discern mechanisms of spontaneous OL regeneration and myelin repair after SCI. Experiments will use a clinically relevant model of spinal contusion to evaluate mechanisms regulating OPC survival, proliferation and differentiation into new OLs after SCI. Without myelin, the ability of spared or regenerating axons to conduct action potentials will be severely hampered or completely blocked. We will use reporter mice and Cre-Lox systems to inhibit glutamate release from axons or specific intracellular signaling molecules to determine if these mechanisms regulate OPC functions after SCI. We will also use a novel model to induce demyelination after SCI to determine if and when OPC repair is greatest or when it is impaired, as our new pilot data suggest it may be impaired over time post-injury. If successful, this project will provide novel insight into how OPCs and myelination are regulated in the adult injured nervous system and may provide new therapeutic targets to improve functional recovery from SCI by enhancing both axon myelination.