Abstract
Under normal conditions, neural stem cells (NSCs or B cells) in the adult subventricular zone (SVZ) give rise to amplifying neural progenitor cells (NPCs or C cells), which can produce neuroblasts (or A cells) that migrate to the olfactory bulb and differentiate into new neurons. However, following brain injury, these cells migrate toward the injury site where they differentiate into astrocytes and oligodendrocytes. In this review, we will focus on recent findings that chronicle how astrocytes and oligodendrocytes derived from SVZ-NSCs respond to different types of injury. We will also discuss molecular regulators of SVZ-NSC proliferation and their differentiation into astrocytes and oligodendrocytes. Overall, the goal of this review is to highlight how SVZ-NSCs respond to injury and to summarize the regulatory mechanisms that oversee their glial response. These molecular and cellular processes will provide critical insights needed to develop strategies to promote brain repair following injury using SVZ-NSCs.
Highlights
IntroductionResearch has begun to unravel complex biological cascades that follows injury to the brain: astroglial activation and proliferation (Pekny et al, 2016, 2019), parenchymal inflammation and infiltration of immune cells (Liesz et al, 2015; Gill and Veltkamp, 2016; Sofroniew, 2020), glial scar formation (Burda et al, 2016), revascularization/re-establishment of blood-brain barrier (Li et al, 2021), remodeling of connections between surviving neurons (Jones, 2017) and replenishment of oligodendrocytes following demyelination injury (Nait-Oumesmar et al, 2007; Butti et al, 2019).Research in this area has revealed new methods to improve and augment these responses after injury
Astrocytes and oligodendrocytes play pivotal roles in diverse injury responses throughout the CNS and the type of injury and location in the brain where the injury occurs dictates their generation by subventricular zone (SVZ)-NSCs
Ischemia and traumatic brain injury (TBI) induce the SVZ to produce astrocytes, whereas oligodendrocytes are produced after white matter injury and demyelinating events
Summary
Research has begun to unravel complex biological cascades that follows injury to the brain: astroglial activation and proliferation (Pekny et al, 2016, 2019), parenchymal inflammation and infiltration of immune cells (Liesz et al, 2015; Gill and Veltkamp, 2016; Sofroniew, 2020), glial scar formation (Burda et al, 2016), revascularization/re-establishment of blood-brain barrier (Li et al, 2021), remodeling of connections between surviving neurons (Jones, 2017) and replenishment of oligodendrocytes following demyelination injury (Nait-Oumesmar et al, 2007; Butti et al, 2019).Research in this area has revealed new methods to improve and augment these responses after injury. Research has begun to unravel complex biological cascades that follows injury to the brain: astroglial activation and proliferation (Pekny et al, 2016, 2019), parenchymal inflammation and infiltration of immune cells (Liesz et al, 2015; Gill and Veltkamp, 2016; Sofroniew, 2020), glial scar formation (Burda et al, 2016), revascularization/re-establishment of blood-brain barrier (Li et al, 2021), remodeling of connections between surviving neurons (Jones, 2017) and replenishment of oligodendrocytes following demyelination injury (Nait-Oumesmar et al, 2007; Butti et al, 2019). Neuroblasts migrate a long-distance (3–8 mm in mice) from the SVZ to the olfactory bulb (Lois and Alvarez-Buylla, 1994; Lois et al, 1996), where they differentiate into granule neurons
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