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| Content Provider | PubMed Central |
|---|---|
| Author | Levison, Steven W. Covey, Matthew V. |
| Abstract | 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. |
| Related Links | http://dx.doi.org/10.1016/j.neuroscience.2007.06.015 |
| Ending Page | 509 |
| Page Count | 9 |
| Starting Page | 501 |
| File Format | |
| ISSN | 03064522 |
| Journal | Neuroscience |
| Issue Number | 2 |
| Volume Number | 148 |
| Language | English |
| Publisher Date | 2007-08-01 |
| Access Restriction | Open |
| Subject Keyword | Neuroscience(all) Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neuroscience |
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