PDF(Pubmed)
Abstract：
Wound healing of the central nervous system (CNS) is characterized by the classical phases of \'hemostasis\', \'inflammation\', \'proliferation\', and \'remodeling\'. Uncontrolled wound healing results in pathological scar formation hindering tissue remodeling and functional recovery in the CNS. Initial blood protein extravasation and activation of the coagulation cascade secure hemostasis in CNS diseases featuring openings in the blood-brain barrier. However, the relevance of blood-derived coagulation factors was overlooked for some time in CNS wound healing and scarring. Recent advancements in animal models and human tissue analysis implicate the blood-derived coagulation factor fibrinogen as a molecular link between vascular permeability and scar formation. In this perspective, we summarize the current understanding of how fibrinogen orchestrates scar formation and highlight fibrinogen-induced signaling pathways in diverse neural and non-neural cells that may contribute to scarring in CNS disease. We particularly highlight a role of fibrinogen in the formation of the lesion border between the healthy neural tissue and the fibrotic scar. Finally, we suggest novel therapeutic strategies via manipulating the fibrinogen-scar-forming cell interaction to improve functional outcomes.
摘要：
中枢神经系统（CNS）的伤口愈合的特点是典型的“止血”阶段，\'炎症\',\'扩散\',和“重塑”。不受控制的伤口愈合导致病理性瘢痕形成,阻碍CNS中的组织重塑和功能恢复。最初的血液蛋白外渗和凝血级联的激活确保了以血脑屏障开口为特征的CNS疾病的止血。然而,血源性凝血因子在中枢神经系统伤口愈合和瘢痕形成中的相关性被忽视了一段时间.动物模型和人体组织分析的最新进展表明，血液来源的凝血因子纤维蛋白原是血管通透性和瘢痕形成之间的分子联系。从这个角度来看,我们总结了目前对纤维蛋白原如何协调瘢痕形成的理解,并强调了纤维蛋白原在多种神经细胞和非神经细胞中诱导的信号通路,这些信号通路可能有助于中枢神经系统疾病的瘢痕形成.我们特别强调了纤维蛋白原在健康神经组织和纤维化瘢痕之间的病变边界形成中的作用。最后,我们建议通过操纵纤维蛋白原-瘢痕形成细胞相互作用来改善功能结局的新治疗策略.
