MicroRNAs in Cerebral Ischemia-Induced Neurogenesis

Abstract

Cerebral ischemia induces neurogenesis including proliferation and differentiation of neural progenitor cells and migration of newly generated neuroblasts. microRNAs (miRNAs) are small non-coding RNAs that decrease gene expression through mRNA destabilization and/or translational repression. Emerging data indicate that miRNAs have a role in mediating processes of proliferation and differentiation of adult neural progenitor cells. This article reviews recent findings on miRNA profile changes in neural progenitor cells after cerebral infarction and the contributions of miRNAs to their ischemia-induced proliferation and differentiation. We highlight interactions between the miR-124 and the miR17-92 cluster and the Notch and Sonic hedgehog signaling pathways in mediating stroke-induced neurogenesis.

Exosomes in stroke pathogenesis and therapy

“…Exosomes are emerging as important intercellular players in mediating neurorestorative events after stroke and neural injury (139)(140)(141). Preliminary work demonstrates that either naturally occurring or engineered exosomes derived from stem/progenitor cells provide therapeutic benefits (139)(140)(141).…”

“…Preliminary work demonstrates that either naturally occurring or engineered exosomes derived from stem/progenitor cells provide therapeutic benefits (139)(140)(141). However, there are multiple unanswered questions and challenges in the development of exosome therapy including the following: (a) identification of the cellular signals by which the ischemic brain is able to affect the content and quantity of exosomes released by brain parenchymal cells and by remote organs, (b) understanding how exosomal cargo affects expression of endogenous genes and proteins in recipient cells of injured brain, (c) delineation of the specific cell types that are targeted by brain parenchymal cell-derived exosomes, and (d) knowledge of the effects of sex, age, and comorbidity on the cellular generation of exosomes and their cargo and the effect of sex, age and comorbidity in response to exosome treatment after stroke.…”

Neurogenesis and Inflammation after Ischemic Stroke: What is Known and Where We Go from Here

“…70,84 Also like the cells in the SGL, those NPCs that do survive migrate out of the SVZ into the striatum and neocortex and mature into functional neurons. 73,[85][86][87][88][89] In addition, it has been demonstrated that transient angiogenesis after stroke allows neuroblasts to migrate along these newly formed blood vessels aiding in their migration out of the SVZ.…”

Function of neural stem cells in ischemic brain repair processes

“…80 Stroke upregulates Shh expression in V/SVZ neural progenitor cells. 81 Inhibition of the Shh pathway reduces proliferation and differentiation of neural progenitor cells, whereas intraventricular infusion of exogenous Shh enhances stroke-induced neurogenesis. 81,82 The bone morphogenic protein (BMP) and Wnt pathways also regulate neurogenesis and oligodendrogenesis.…”

“…81 Inhibition of the Shh pathway reduces proliferation and differentiation of neural progenitor cells, whereas intraventricular infusion of exogenous Shh enhances stroke-induced neurogenesis. 81,82 The bone morphogenic protein (BMP) and Wnt pathways also regulate neurogenesis and oligodendrogenesis. Overexpression of BMP7 in ependymal cells inhibits neural progenitor cell proliferation and neuroblast production.…”