摘要The limited ability of the central nervous system (CNS) to regenerate in adult mammals after injury or disease is a significant problem. Intriguingly, neural stem/progenitor cells (NSPCs) offer great promise for regenerating the CNS. Endogenous or transplanted NSPCs contribute to repair processes, but their differentiation and function are abnormal in CNS injury and disease. The main reasons for these abnormalities are changes in the extracellular environment in the injured CNS that affect signaling pathways and transcriptional regulation in NSPCs. In CNS disease with vascular permeability or blood-brain barrier disruption, blood-derived fibrinogen enters the parenchyma and drastically changes the extracellular environment of brain cells, including NSPCs. Fibrinogen is present in the brain in a wide range of CNS pathologies, such as multiple sclerosis, Alzheimer's disease, stroke, and traumatic brain injury. Here, within this perspective, we focus on how the blood-derived coagulation factor fibrinogen alters the subventricular zone (SVZ) stem cell niche environment to activate the bone morphogenetic protein (BMP) receptor (BMPR) signaling pathway in NSPCs. The activated BMPR signaling increases p75 neurotrophin receptor (p75NTR) and inhibitor of DNA binding 3 (Id3) abundance in NSPCs, and thus, regulates NSPC migration and differentiation in a mouse model of cortical ischemic stroke (photothrombotic ischemia) and cortical brain trauma (stab wound injury) (Pous et al., 2020; Deshpande et al., 2021). NSPCs located in the adult mammalian SVZ are an endogenous source for cell replacement and brain repair. The fine-tuned cellular and molecular niche environment controls the cardinal features of the SVZ NSPCs: an unlimited capacity for self-renewal, indefinite ability to proliferate, and multipotency for the different neuroectodermal lineages of the CNS. Pathological states induce dynamic changes in this niche and trigger a regenerative response, but the regulatory mechanisms that control NSPC differentiation in CNS disease are largely unknown. In contrast to the human brain SVZ, where production of new neurons is highly reduced by 2 years of age and little to no neurogenesis is observed after childhood, the adult rodent brain SVZ continuously produces new neurons throughout life and reacts to CNS injury and disease. Therefore, the adult rodent SVZ is ideally suited for studying cellular signaling cascades and transcriptional programs in adult NSPCs and for identifying potential pharmacological and regenerative cell-based therapies for neuronal regeneration. Improved control of the endogenous or transplanted NSPC fate and functions will provide optimized therapeutic effects by replacement of lost neurons and severed axons and creation of a permissive microenvironment to promote CNS tissue repair.