CD24在创伤性脑损伤后神经修复中的作用机制研究

Neuronal repair is a key regulator of prognosis in patients with traumatic brain injury (TBI), however, the specific mechanisms have not been well elucidated. We previously found that the elevated cortical CD24 could negatively regulate the non-infectious inflammatory response following TBI. Meanwhile, we occasionally found that CD24 was upregulated not only in glial cells but also in neurons. Accordingly, we speculated that CD24 might play an important role in some others fields as well as in inflammatory response. Therefore, we performed our pre-experiments and found that CD24 was upregulated much earlier in neurogenesis areas (hippocampal dentate gyrus and subventricular zone) than that in cerebral cortex surrounding injury. Based on the latest research in the world, we raised a hypothesis that the neurogenesis could be activated after TBI, and neural stem cells had a increased proliferation, diferentiation and imigration. CD24, as a marker of these cells, could be elevated in the brain, thus contributing to the neuronal repair following TBI. In this study, we are planning to apply RNA interference and gene overexxpression aiming at CD24 to investigate the mechanisms of CD24 in neuronal repair following TBI, which will be validated through neuronal regenerative pattern both in vivo and in vitro. From this research, we expect to better understand the specific pattern and mechanisms of neuronal repair after TBI, thereby providing a novel therapeutic target for TBI.

创伤性脑损伤（TBI）后神经修复是影响患者预后的重要因素，但其具体机制仍不明确。我们研究发现：TBI后损伤皮层CD24表达增高，并可以负向调控炎性反应；同时发现除胶质细胞外，神经元中CD24也明显上调。我们推测CD24在TBI后可能不只是参与调控炎性反应，同时具有其他重要功能。对此，我们预实验发现TBI后神经发生区域（海马齿状回和室管膜下区）内CD24同样被上调，且表达时相明显早于损伤皮层。结合国际最新研究，我们提出假说：TBI后脑内神经发生区域中的神经干细胞发生增殖、分化和迁移，而CD24作为其潜在标志物可在脑内各区域全面上调，最终在神经修复中发挥重要作用。本课题拟通过体内、体外实验，针对CD24运用RNA干扰及基因过表达技术，立足神经再生模式，探讨CD24在TBI后神经修复中的作用机制。通过此项研究，将有助于深入理解TBI后神经修复的具体模式与机制，为TBI临床治疗与康复提供新的靶点。

创伤性脑损伤（TBI）后神经修复是影响患者预后的重要因素，但其具体机制仍不明确。前期研究发现：TBI后损伤皮层CD24表达显著增高，并可以负向调控无菌性炎性反应；同时发现除胶质细胞外，神经元中CD24也明显上调。我们推测CD24在TBI后可能不只是参与调控炎性反应，同时具有其他重要功能。同时，我们预实验发现TBI后神经发生区域（海马齿状回）CD24同样被上调，且表达时相明显早于损伤皮层。结合国际最新研究，我们提出假说：TBI后脑内神经发生区域中的神经干细胞发生增殖、分化和迁移，而CD24作为其潜在标志物可在脑内各区域全面上调，最终在神经修复中发挥重要作用。本课题通过体内、体外实验，针对CD24运用RNA干扰技术，立足神经再生模式，探讨CD24在TBI后神经修复中的作用机制。实验结果发现：TBI后CD24显著增高，下调CD24不但可以放大TBI后的无菌性炎性反应，同时显著抑制TBI后的神经修复、加重TBI后的神经损伤，提示CD24在TBI后脑内炎性反应和神经修复调控中发挥着重要作用。通过此项研究，将有助于深入理解TBI后神经修复的具体模式与机制，为TBI临床治疗与康复提供新的靶点。