Neural Stem Cells in the Subventricular Zone are Resilient to Hypoxia/Ischemia whereas Progenitors are Vulnerable

Romanko, Michael J.; Rothstein, Raymond; Levison, Steven W.

doi:10.1097/01.wcb.0000123906.17746.00

Cited by 100 publications

(74 citation statements)

References 49 publications

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“…One consideration for the differences in cell proliferation between the medial and lateral portions of the SVZ is the cell death that occurs after injury. Our laboratory has demonstrated recently that cell death is uncommon in the medial region compared with the lateral SVZ (Romanko et al, 2004). Thus, proliferation may be increased within the lateral compartment as well but offset by extensive cell death.…”

Section: Discussionmentioning

confidence: 98%

Neural Stem/Progenitor Cells Participate in the Regenerative Response to Perinatal Hypoxia/Ischemia

Felling¹,

Snyder²,

Romanko³

et al. 2006

J. Neurosci.

171

166

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Perinatal hypoxia/ischemia (H/I) is the leading cause of neurologic injury resulting from birth complications. Recent advances in critical care have dramatically improved the survival rate of infants suffering this insult, but ϳ50% of survivors will develop neurologic sequelae such as cerebral palsy, epilepsy or cognitive deficits. Here we demonstrate that tripotential neural stem/progenitor cells (NSPs) participate in the regenerative response to perinatal H/I as their numbers increase 100% by 3 d and that they alter their intrinsic properties to divide using expansive symmetrical cell divisions. We further show that production of new striatal neurons follows the expansion of NSPs. Increased proliferation within the NSP niche occurs at 2 d after perinatal H/I, and the proliferating cells express nestin. Of those stem-cell related genes that change, the membrane receptors Notch1, gp-130, and the epidermal growth factor receptor, as well as the downstream transcription factor Hes5, which stimulate NSP proliferation and regulate stem cellness are induced before NSP expansion. The mechanisms for the reactive expansion of the NSPs reported here reveal potential therapeutic targets that could be exploited to amplify this response, thus enabling endogenous precursors to restore a normal pattern of brain development after perinatal H/I.

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Section: Discussionmentioning

confidence: 98%

Neural Stem/Progenitor Cells Participate in the Regenerative Response to Perinatal Hypoxia/Ischemia

Felling¹,

Snyder²,

Romanko³

et al. 2006

J. Neurosci.

171

166

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show abstract

“…Unfortunately, this idea does not appear to hold true. Severe hypoxia-ischemia in neonatal rat or mouse actually depletes the SVZ progenitor pool (Brazel et al, 2004;Romanko et al, 2004). This depletion likely impairs the generation of neurons and glia from the postnatal SVZ.…”

Section: Agementioning

confidence: 99%

Adult Neurogenesis and the Ischemic Forebrain

Lichtenwalner

Parent

2005

J Cereb Blood Flow Metab

261

190

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The recent identification of endogenous neural stem cells and persistent neuronal production in the adult brain suggests a previously unrecognized capacity for self-repair after brain injury. Neurogenesis not only continues in discrete regions of the adult mammalian brain, but new evidence also suggests that neural progenitors form new neurons that integrate into existing circuitry after certain forms of brain injury in the adult. Experimental stroke in adult rodents and primates increases neurogenesis in the persistent forebrain subventricular and hippocampal dentate gyrus germinative zones. Of greater relevance for regenerative potential, ischemic insults stimulate endogenous neural progenitors to migrate to areas of damage and form neurons in otherwise dormant forebrain regions, such as the neostriatum and hippocampal pyramidal cell layer, of the mature brain. This review summarizes the current understanding of adult neurogenesis and its regulation in vivo, and describes evidence for stroke-induced neurogenesis and neuronal replacement in the adult. Current strategies used to modify endogenous neurogenesis after ischemic brain injury also will be discussed, as well as future research directions with potential for achieving regeneration after stroke and other brain insults.

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“…Hypoxic/ischemic (H/I) insults, in both preterm and term infants, remain a major cause of structural and functional brain abnormalities. Previously it was thought impossible to achieve any kind of meaningful recovery after a perinatal brain injury, however, there is increasing evidence that the brain contains neural stem cells, that are resilient to H/I insults (Romanko et al, 2004). Moreover, there is emerging evidence that there is neuronal and glial cell replacement from these resident precursors (Parent et al, 2002,Yang and.…”

Section: Introductionmentioning

confidence: 99%

“…After H/I there is an initial depletion of progenitors, followed by repopulation, that results in an increase in the size of the SVZ during recovery (Levison et al, 2001,Plane et al, 2004,Romanko et al, 2004,Ong et al, 2005. Felling et al (2006) observed increased proliferation in the SVZ two days after H/I resulting in an increase in precursors that persists for a week or more (Plane et al, 2004,Yang and.…”

Section: Introductionmentioning

confidence: 99%

Leukemia inhibitory factor participates in the expansion of neural stem/progenitors after perinatal hypoxia/ischemia

Covey

Levison

2007

Neuroscience

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Subsequent to perinatal hypoxia/ischemia there is an increase in the number of neural stem/progenitor cells (NSP) within the subventricular zone. Gene expression analyses have implicated Notch signaling in the expansion of these tripotential cells but there are limited data as to which signals are stimulating Notch activation. There is evidence that the LIFR/gp130 receptor heterodimer induces Notch1 to maintain NSP populations during normal development. LIF and CNTF bind to these receptor components and they coordinate injury responses in the CNS. Therefore, the aim of these studies was to investigate whether CNTF and/or LIF participate in NSP expansion in the SVZ after H/I as well as to characterize the downstream events that regulate NSP numbers. We report that LIF mRNA is induced 48 hours post insult by 13 fold but that it returns almost to baseline by 72 hours. Commensurate with increased LIF expression there is a corresponding increase in phosphorylated STAT-3 within the SVZ. Modeling the changes that occur in vivo, we show that LIF induces STAT-3 phosphorylation in neurospheres to enhance Delta-like-1 and Notch1 expression as well as to increase Notch1 activation. LIF also expands neurosphere number and size in vitro. Whereas CNTF can mimic the effects of LIF in vitro, CNTF expression in the SVZ was unchanged during recovery from H/I. Cumulatively, these data implicate LIF and not CNTF in the expansion of NSPs in the SVZ after perinatal brain injury. As both LIF expression and the endogenous regenerative response after brain injury are time-delimited, these findings provide insights into strategies to expand the endogenous pool of NSPs to repopulate the damaged brain.

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Neural Stem Cells in the Subventricular Zone are Resilient to Hypoxia/Ischemia whereas Progenitors are Vulnerable

Cited by 100 publications

References 49 publications

Neural Stem/Progenitor Cells Participate in the Regenerative Response to Perinatal Hypoxia/Ischemia

Neural Stem/Progenitor Cells Participate in the Regenerative Response to Perinatal Hypoxia/Ischemia

Adult Neurogenesis and the Ischemic Forebrain

Leukemia inhibitory factor participates in the expansion of neural stem/progenitors after perinatal hypoxia/ischemia

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