Update on the Interaction of Notch and Wnt/Β-Catenin Signaling in Neural Stem Cells and Brain Homeostasis During Ischemic Stroke Publisher Pubmed



Moghadam M H ; Mohammdnejad D ; Rahbarghazi R ; Mahmoudi J ; Hassanzadeh A ; Mafikandi V ; Nasrabadi H T ; Karimipour M
Source: Tissue and Cell Published:2026

Abstract

Stroke is the second leading cause of death globally and a major contributor to long-term disability. Neural stem cells (NSCs) offer a promising therapeutic strategy for ischemic conditions by modulating neuroinflammation, enhancing neuroplasticity, facilitating tissue remodeling, and promoting neural tissue regeneration. Preclinical evidence strongly indicates that NSCs migrate to damaged brain regions and play a crucial role in repair by differentiating into various functional neural cell types. Recent research has underscored the significance of specific molecular pathways, particularly the Wnt/β-catenin and Notch signaling pathways, in determining NSC fate. These pathways are essential for orchestrating key intracellular transcription factor expression and for regulating mechanisms that govern NSC function. They influence the secretion of critical factors from both NSCs and the surrounding cells, exhibiting opposing effects on neuronal differentiation and cellular fate. This dual nature of signaling pathways is vital for synchronizing the expression of proneural genes while also regulating fundamental processes such as self-renewal, differentiation, and growth in response to hypoxic or ischemic conditions. This review aims to elucidate the intricate signaling mechanisms that govern NSC fate after ischemic stroke, with a focus on the Notch and Wnt/β-catenin pathways. A deeper understanding of these mechanisms could pave the way for new therapeutic interventions that significantly enhance structural integrity, promote neural repair, improve functional recovery, and maintain brain homeostasis in stroke patients. © 2026