Neurogenesis After Stroke: A Therapeutic Perspective

Abstract

Stroke is a major cause of death and disability worldwide. Yet therapeutic strategies available to treat stroke are very limited. There is an urgent need to develop novel therapeutics that can effectively facilitate functional recovery. The injury that results from stroke is known to induce neurogenesis in penumbra of the infarct region. There is considerable interest in harnessing this response for therapeutic purposes. This review summarizes what is currently known about stroke-induced neurogenesis and the factors that have been identified to regulate it. Additionally, some key studies in this field have been highlighted and their implications on future of stroke therapy have been discussed. There is a complex interplay between neuroinflammation and neurogenesis that dictates stroke outcome and possibly recovery. This highlights the need for a better understanding of the neuroinflammatory process and how it affects neurogenesis, as well as the need to identify new mechanisms and potential modulators. Neuroinflammatory processes and their impact on post-stroke repair have therefore also been discussed.

SARS-CoV-2 mediated neuroinflammation and the impact of COVID-19 in neurological disorders

“…SARS-CoV-2 may also use integrins in host cell entry through its conserved RGD (403–405: Arg-Gly-Asp) motif in its trimeric spike proteins [ 43 ]. Integrins, a family of cell-surface receptors, are composed of non-covalently linked α and β subunits that recognize and bind to extracellular matrix (ECM) proteins and mediate cell survival, proliferation, differentiation, and migration [ [44] , [45] , [46] ]. Deregulated cell-cell and cell-matrix interactions promote tumor growth, metastasis, and tumor angiogenesis.…”

Post-stroke Neurogenesis: Friend or Foe?

“…Another factors identified after stroke and which might directly affect NSC proliferation are, among others, fibroblast growth factor-2 (FGF-2) (Yoshimura et al, 2001(Yoshimura et al, , 2003, insulin-like growth factor-1 (IGF-1) (Yan et al, 2006) and brain-derived neurotrophic factor (BDNF) (Chen et al, 2005). Furthermore, several mediators like SDF-1α, MCP-1, and matrix metalloproteinases (MMP) have been implicated in influencing neuroblast positioning and extracellular matrix remodeling (Rahman et al, 2020). (3) Another influence to be considered is the inflammatory response elicited by the injured brain, whereby astrocytes and microglia activation could lead to the secretion of a variety of growth factors and immune modulators able to affect progenitor proliferation and survival.…”

BMS-986020, a Specific LPA1 Antagonist, Provides Neuroprotection against Ischemic Stroke in Mice

“…Newly born neurons can act as neuronal reservoirs to prevent disease pathogenesis in post-ischemic brains, at least in part [33]. Moreover, it is believed that potentiation of neurogenesis using exogenous intervention could be a desirable strategy for recovery after ischemic challenge [34,35]. To determine whether BMS administration could potentiate tMCAO-induced neurogenesis, we performed double immunofluorescence staining for newly born neurons with DCX and BrdU.…”