The general long-term goal of this project is to identify the effects of brain injury on endogenous neural stem cells (NSCs). Specifically this proposal aims to identify the acute response of these NSCs to a perinatal hypoxic/ischemic (H/I) brain insult. Once defined, this response could provide a potential therapeutic target for preventing consequence of perinatal H/I such as cerebral palsy, mental retardation, and a spectrum of other neurological disorders. NSCs are known to reside as a quiescent population of cells in the subventricular zone (SVZ) throughout life. These cells can be induced to proliferate both in vitro and in vivo with specific growth factors. We have observed that NSCs are more abundant in dissociated cultures of the SVZ after H/I; therefore, the immediate goal is to define the acute effects of perinatal H/I on SVZ NSCs. My central hypothesis is that perinatal H/I recruits NSCs to a more proliferative state, thereby expanding the total population. I will determine the effect of H/I on levels of growth factors and their receptors in the SVZ as well as the dose-response of NSCs to these growth factors after H/I. I will also determine the effects of H/I on the proliferation kinetics and mode of division of NSCs. These experiments can potentially identify a novel target for therapeutic strategies in perinatal brain injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31NS046903-01
Application #
6692264
Study Section
Special Emphasis Panel (ZRG1-F01 (20))
Program Officer
Chiu, Arlene Y
Project Start
2003-07-01
Project End
2006-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
1
Fiscal Year
2003
Total Cost
$24,598
Indirect Cost
Name
Pennsylvania State University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033
Felling, Ryan J; Covey, Matthew V; Wolujewicz, Paul et al. (2016) Astrocyte-produced leukemia inhibitory factor expands the neural stem/progenitor pool following perinatal hypoxia-ischemia. J Neurosci Res 94:1531-1545
Alagappan, Dhivyaa; Lazzarino, Deborah A; Felling, Ryan J et al. (2009) Brain injury expands the numbers of neural stem cells and progenitors in the SVZ by enhancing their responsiveness to EGF. ASN Neuro 1: