Oligodendrogenesis after cerebral ischemia

Abstract

Neural stem cells in the subventricular zone (SVZ) of the lateral ventricle of adult rodent brain generate oligodendrocyte progenitor cells (OPCs) that disperse throughout the corpus callosum and striatum where some of OPCs differentiate into mature oligodendrocytes. Studies in animal models of stroke demonstrate that cerebral ischemia induces oligodendrogenesis during brain repair processes. This article will review evidence of stroke-induced proliferation and differentiation of OPCs that are either resident in white matter or are derived from SVZ neural progenitor cells and of therapies that amplify endogenous oligodendrogenesis in ischemic brain.

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.…”

Thymosin β4 as a restorative/regenerative therapy for neurological injury and neurodegenerative diseases

“…Diabetes, MS, TBI and stroke evoke demyelination and white matter damage, which result in neurological deficits. OLGs also maintain the structure of the CNS and their abundant presence in brain retards cerebral atrophy [5]. Thus, Tb4 that promotes generation and differentiation of OPCs and thereby increases OLGs and myelination contributes to the improvement of neurological recovery found in multiple animal models of neurological injury and neurodegenerative disease [7,9,10].…”

“…Cell-based therapy, for example, stimulates the generation of angiogenic factors that promote vascular remodeling, and the activated and newly formed endothelial cells act as a source of trophic factors, that also enhance neurogenesis within the subventricular zone (SVZ) and neurite outgrowth. The newly formed cells migrate from the SVZ to the region of injury, interact with activated vasculature and differentiate into neurons and oligodendrocytes (OLGs) [3][4][5]. This restorative tapestry of events creates a supportive environment for neurovascular plasticity, neurite outgrowth and myelination of axons.…”

The ventricular-subventricular zone: a source of oligodendrocytes in the adult brain

“…These factors appear to decrease by aging and compromise the efficiency of remyelination into the brain. In the chapter 9, significant questions and hypotheses regarding this topic are analyzed by Agathou et al (2013) that indicates that a pathological condition as stroke can increase oligodendrogenesis in the white matter and V-SVZ during brain repair (Zhang et al, 2013), which support the notion that many inflammatory cytokines regulate the V-SVZ cells (Gonzalez-Perez et al, 2012). In summary, growing evidence indicates that V-SVZ NSCs are good candidates to establish stem cell-based therapies in demyelinating disorders.…”