Delayed IGF-1 Administration Rescues Oligodendrocyte Progenitors from Glutamate-Induced Cell Death and Hypoxic-Ischemic Brain Damage

Wood, Teresa L.; Loladze, Vaho; Altieri, Stefanie C.; Gangoli, Nitish; Levison, Steven W.; Brywe, Katarina G; Mallard, Carina; Hagberg, Henrik

doi:10.1159/000105471

Cited by 63 publications

(48 citation statements)

References 99 publications

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“…Post-transcriptional control by microRNAs regulates OL differentiation and OPCs that lack mature microRNAs display arrested maturation (Dugas et al 2010; Shin et al 2009). Insulin-like growth factors (IGFs) promote OL lineage cell survival and myelination and protect against OL progenitor loss in fetal and neonatal models of WMI (Guan et al 2001; Pang et al 2010b; Wood et al 2007). Bone morphogenetic proteins both repress OL differentiation and regulate myelin protein expression (See et al 2004; See and Grinspan 2009).…”

Section: Cellular-molecular Mechanisms Of Acute Wmimentioning

confidence: 99%

Pathophysiology of glia in perinatal white matter injury

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Rosenberg

2014

Glia

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155

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Injury to the preterm brain has a particular predilection for cerebral white matter. White matter injury (WMI) is the most common cause of brain injury in preterm infants and a major cause of chronic neurological morbidity including cerebral palsy. Factors that predispose to WMI include cerebral oxygenation disturbances and maternal-fetal infection. During the acute phase of WMI, pronounced oxidative damage occurs that targets late oligodendrocyte progenitors (preOLs). The developmental predilection for WMI to occur during prematurity appears to be related to both the timing of appearance and regional distribution of susceptible preOLs that are vulnerable to a variety of chemical mediators including reactive oxygen species, glutamate, cytokines, and adenosine. During the chronic phase of WMI, the white matter displays abberant regeneration and repair responses. Early OL progenitors responds to WMI with a rapid robust proliferative response that results in a several fold regeneration of preOLs that fail to terminally differentiate along their normal developmental time course. PreOL maturation arrest appears to be related in part to inhibitory factors that derive from reactive astrocytes in chronic lesions. Recent high field MRI data support that three distinct forms of chronic WMI exist, each of which displays unique MRI and histopathological features. These findings suggest the possibility that therapies directed at myelin regeneration and repair could be initiated early after WMI and monitored over time. These new mechanisms of acute and chronic WMI provide access to a variety of new strategies to prevent or promote repair of WMI in premature infants.

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Section: Cellular-molecular Mechanisms Of Acute Wmimentioning

confidence: 99%

Pathophysiology of glia in perinatal white matter injury

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Rosenberg

2014

Glia

166

155

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“…Insulin-like growth factors promote OL lineage cell survival and myelination and protect against OL progenitor loss in fetal and neonatal models of WMI. 87-89 Definition of the mechanisms that link these inhibitory pathways to trigger myelination failure will be critical to develop new regeneration and repair therapies for neonatal WMI and other chronic myelin disorders that include multiple sclerosis and vascular dementia.…”

Section: Pathogenesis Of White Matter Injurymentioning

confidence: 99%

Brain Injury in the Preterm Infant: New Horizons for Pathogenesis and Prevention

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2015

Pediatric Neurology

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Preterm neonates are surviving with a milder spectrum of motor and cognitive disabilities that appear to be related to widespread disturbances in cell maturation that target cerebral gray and white matter. Whereas the preterm brain was previously at high risk for destructive lesions, preterm survivors now commonly display less severe injury that is associated with aberrant regeneration and repair responses that result in reduced cerebral growth. Impaired cerebral white matter growth is related to myelination disturbances that are initiated by acute death of pre-myelinating oligodendrocytes (preOLs), but are followed by rapid regeneration of preOLs that fail to normally mature to myelinating cells. Although immature neurons are more resistant to cell death than mature neurons, they display widespread disturbances in maturation of their dendritic arbors and synapses, which further contributes to impaired cerebral growth. Thus, even more mild cerebral injury involves disrupted repair mechanisms in which neurons and preOLs fail to fully mature during a critical window in development of neural circuitry. These recently recognized distinct forms of cerebral gray and white matter dysmaturation raise new diagnostic challenges and suggest new therapeutic strategies to promote brain growth and repair.

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“…The fact that IGF-I was neuroprotective supports the view that beneficial effects of the IGFs in the context of neonatal H–I will extend beyond their effects on the NPs of the SVZ. For example, Wood et al (16) demonstrated that infusing IGF-I into neonatal rat pups acutely after H–I increased the number of oligodendrocyte progenitor cells (OPC) in white matter (16). …”

Section: Discussionmentioning

confidence: 99%

Insulin-Like Growth Factor Receptor Signaling is Necessary for Epidermal Growth Factor Mediated Proliferation of SVZ Neural Precursors in vitro Following Neonatal Hypoxiaâ€“Ischemia

et al. 2014

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In this study, we assessed the importance of insulin-like growth factor (IGF) and epidermal growth factor (EGF) receptor co-signaling for rat neural precursor (NP) cell proliferation and self-renewal in the context of a developmental brain injury that is associated with cerebral palsy. Consistent with previous studies, we found that there is an increase in the in vitro growth of subventricular zone NPs isolated acutely after cerebral hypoxia–ischemia; however, when cultured in medium that is insufficient to stimulate the IGF type 1 receptor, neurosphere formation and the proliferative capacity of those NPs was severely curtailed. This reduced growth capacity could not be attributed simply to failure to survive. The growth and self-renewal of the NPs could be restored by addition of both IGF-I and IGF-II. Since the size of the neurosphere is predominantly due to cell proliferation we hypothesized that the IGFs were regulating progression through the cell cycle. Analyses of cell cycle progression revealed that IGF-1R activation together with EGFR co-signaling decreased the percentage of cells in G1 and enhanced cell progression into S and G2. This was accompanied by increases in expression of cyclin D1, phosphorylated histone 3, and phosphorylated Rb. Based on these data, we conclude that coordinate signaling between the EGF receptor and the IGF type 1 receptor is necessary for the normal proliferation of NPs as well as for their reactive expansion after injury. These data indicate that manipulations that maintain or amplify IGF signaling in the brain during recovery from developmental brain injuries will enhance the production of new brain cells to improve neurological function in children who are at risk for developing cerebral palsy.

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Delayed IGF-1 Administration Rescues Oligodendrocyte Progenitors from Glutamate-Induced Cell Death and Hypoxic-Ischemic Brain Damage

Cited by 63 publications

References 99 publications

Pathophysiology of glia in perinatal white matter injury

Pathophysiology of glia in perinatal white matter injury

Brain Injury in the Preterm Infant: New Horizons for Pathogenesis and Prevention

Insulin-Like Growth Factor Receptor Signaling is Necessary for Epidermal Growth Factor Mediated Proliferation of SVZ Neural Precursors in vitro Following Neonatal Hypoxiaâ€“Ischemia

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