Mechanisms of Mouse Neural Precursor Expansion after Neonatal Hypoxia-Ischemia

Kd, Buono; Goodus, Matthew T.; M, Guardia Clausi; Jiang, Yuhui; Loporchio, Dean; Levison, Steven W.

doi:10.1523/jneurosci.2868-12.2015

Cited by 38 publications

(53 citation statements)

References 52 publications

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“…65,66 OPCs are vulnerable to perinatal H/I injury, leading to permanent white matter damage. 17,55 Fluorescence-activated cell sorting (FACS) analysis of perinatal V/SVZ neural progenitor cells reveals the presence of a heterogeneous population of NG2 (a marker of OPCs) positive neural progenitor cells, and that perinatal H/I injury promotes proliferation of subpopulations of NG2 positive neural progenitor cells. 17 These data suggest that perinatal V/SVZ neural progenitor cells generate OPCs in response to perinatal H/I injury.…”

Section: Perinatal H/i Injury and Stroke-induced Oligodendrogenesismentioning

confidence: 99%

“…17,55 Fluorescence-activated cell sorting (FACS) analysis of perinatal V/SVZ neural progenitor cells reveals the presence of a heterogeneous population of NG2 (a marker of OPCs) positive neural progenitor cells, and that perinatal H/I injury promotes proliferation of subpopulations of NG2 positive neural progenitor cells. 17 These data suggest that perinatal V/SVZ neural progenitor cells generate OPCs in response to perinatal H/I injury. However, OPCs within the V/SVZ do not migrate toward H/I injured brain regions, while increased OPCs in the injured striatum originate from proliferating OPCs within the striatum.…”

Section: Perinatal H/i Injury and Stroke-induced Oligodendrogenesismentioning

confidence: 99%

“…[12][13][14][15][16] Perinatal H/I injury induces acute neurogenesis. 17 Focal cerebral ischemia in the adult rodent promotes neurogenesis primarily in the V/SVZ and induces neuroblast migration from the V/SVZ to the ischemic boundary. 13,14,[18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] Newly generated neuroblasts are involved in functional recovery after stroke.…”

Section: Introductionmentioning

confidence: 99%

“…12,39,[42][43][44] Perinatal H/I injury induces proliferation of neural stem and progenitor cells as well as neuroblasts in the V/SVZ. [45][46][47] Using a multimarker flow cytometry approach, a study shows that perinatal H/I injury promotes neural progenitor cell proliferation, but reduces neural stem cell generation of neural progenitor cells, 17 which may contribute to transient neurogenesis induced by perinatal H/I injury (Table 1).…”

Section: Introductionmentioning

confidence: 99%

“…13,[17][18][19]22,46 Studies based on clonal analysis and whole-mount tissue preparation of the adult rodent brain demonstrate that in the non-ischemic V/SVZ, neural progenitor cells are actively dividing with a cell cycle ranging from 18 to 25 h, and doublecortin (DCX) positive neuroblasts have a cell cycle length of 18 h. 59,60 The progenitor cells divide 3 times before converting into neuroblasts while neuroblasts undergo one to two time divisions prior to migrating out the V/ SVZ. 43,61 Stroke transiently increases the percentage of dividing neural progenitor cells from 15 to 21% in non-ischemic V/SVZ to 31%.…”

Section: Introductionmentioning

confidence: 99%

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Function of neural stem cells in ischemic brain repair processes

Zhang

Chopp

2016

J Cereb Blood Flow Metab

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Hypoxic/ischemic injury is the single most important cause of disabilities in infants, while stroke remains a leading cause of morbidity in children and adults around the world. The injured brain has limited repair capacity, and thereby only modest improvement of neurological function is evident post injury. In rodents, embryonic neural stem cells in the ventricular zone generate cortical neurons, and adult neural stem cells in the ventricular-subventricular zone of the lateral ventricle produce new neurons through animal life. In addition to generation of new neurons, neural stem cells contribute to oligodendrogenesis. Neurogenesis and oligodendrogenesis are essential for repair of injured brain. Much progress has been made in preclinical studies on elucidating the cellular and molecular mechanisms that control and coordinate neurogenesis and oligodendrogenesis in perinatal hypoxic/ischemic injury and the adult ischemic brain. This article will review these findings with a focus on the ventricular-subventricular zone neurogenic niche and discuss potential applications to facilitate endogenous neurogenesis and thereby to improve neurological function post perinatal hypoxic/ischemic injury and stroke.

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Section: Perinatal H/i Injury and Stroke-induced Oligodendrogenesismentioning

confidence: 99%

Section: Perinatal H/i Injury and Stroke-induced Oligodendrogenesismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Function of neural stem cells in ischemic brain repair processes

Zhang

Chopp

2016

J Cereb Blood Flow Metab

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Olig1 is required for noggin‐induced neonatal myelin repair

Sabo

Heine

Schirmer

et al. 2017

Annals of Neurology

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Objective Neonatal white matter injury (NWMI) is a lesion found in preterm infants that can lead to cerebral palsy. Although antagonists of bone morphogenetic protein (BMP) signaling, such as Noggin, promote oligodendrocyte precursor cell (OPC) production after hypoxic-ischemic injury, the downstream functional targets are poorly understood. The bHLH protein Olig1 promotes oligodendrocyte (OL) development and is essential during remyelination in adult mice. Here, we investigated whether Olig1 function is required downstream of BMP antagonism for the response to injury in the neonatal brain. Methods We used wild type and Olig1 mutant mice subjected to neonatal stroke and postnatal neural progenitor cultures, and we analyzed Olig1 expression in human postmortem samples from neonates that suffered hypoxic-ischemic encephalopathy (HIE). Results Olig1-null neonatal mice showed significant hypomyelination after moderate neonatal stroke. Surprisingly, damaged white matter tracts in Olig1−/− mice lacked Olig2+ OPCs and instead proliferating neuronal precursors and GABAergic interneurons were present. We demonstrate that Noggin-induced OPC production requires Olig1 function. In postnatal neural progenitors, Noggin governs production of OLs versus interneurons through Olig1-mediated repression of Dlx1/2 transcription factors. Additionally, we observed that Olig1 and the BMP signaling effector pSMAD1/5/8 are elevated in the subventricular zone (SVZ) of human infants with HIE compared to controls. Interpretation These findings indicate that Olig1 has a critical function in the regulation of the postnatal neural progenitor cell production in response to Noggin.

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Astrocyte‐produced leukemia inhibitory factor expands the neural stem/progenitor pool following perinatal hypoxia–ischemia

Felling

Covey²,

Wolujewicz³

et al. 2016

J of Neuroscience Research

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Brain injuries, such as cerebral hypoxia-ischemia (H–I), induce a regenerative response from the neural stem/progenitors (NSPs) of the subventricular zone (SVZ); however, the mechanisms that regulate this expansion have not yet been fully elucidated. The Notch-DSL signaling pathway is considered essential for the maintenance of neural stem cells, but it is not known if it is necessary for the expansion of the NSPs subsequent to perinatal H–I injury. Therefore, the aim of this study was to investigate whether this pathway contributes to NSP expansion in the SVZ after H–I and if so, to establish whether this pathway is directly induced by H–I or regulated by paracrine factors. Here we report that Notch1 receptor induction and one of its ligands, Delta-like 1 precedes NSP expansion after perinatal hypoxia-ischemia in P6 rat pups and that this increase occurs specifically in the most medial cell layers of the SVZ where the stem cells reside. Pharmacologically inhibiting Notch signaling in vivo diminished NSP expansion. With an in vitro model of H–I, Notch1 was not induced directly by hypoxia, but was stimulated by soluble factors, specifically leukemia inhibitory factor, produced by astrocytes within the SVZ. These data confirm the importance both of the Notch-DSL signaling pathway in the expansion of NSPs after H–I and in the role of the support cells in their niche. They further support the body of evidence that indicates that leukemia inhibitory factor is a key injury induced cytokine that is stimulating the regenerative response of the NSPs.

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Mechanisms of Mouse Neural Precursor Expansion after Neonatal Hypoxia-Ischemia

Abstract: Neonatal hypoxia-ischemia (H-I

Cited by 38 publications

References 52 publications

Function of neural stem cells in ischemic brain repair processes

Function of neural stem cells in ischemic brain repair processes

Olig1 is required for noggin‐induced neonatal myelin repair

Astrocyte‐produced leukemia inhibitory factor expands the neural stem/progenitor pool following perinatal hypoxia–ischemia

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