Spinal cord injury (SCI) is a serious ailment, seriously crippling those affected, and costing our nation some 20 billion dollars each year. The central nervous system (CNS) is not thought to repair itself after injury, but instead, it undergoes substantial secondary injury resulting in larger, more debilitating lesions. Tumor necrosis factor alpha (TNFa) and glutamate - both molecules released in high concentrations after SCI - appear to act synergistically in bringing about rapid cell death in spinal cord gray matter, as TNFa upregulates glutamate receptors on the neuronal cell surface. However, it is not yet known what effects, if any, the excitotoxic release of TNFa and glutamate has on the surrounding white matter, and what role these molecules play in the expanding lesion of secondary cell death. Oligodendrocytes (oligos) in the white matter are known to be particularly sensitive to secondary cell death after SCI, upregulating expression of the p75 """"""""death"""""""" receptor. Thus, oligo reaction to TNFa and glutamate-agonists will be examined with the hypotheses that: 1) TNFa potentiates the excitotoxic effect of glutamate-agonists on oligos in vivo, 2) TNFa increases localization of glutamate receptors to the oligo cell surface, and 3) low doses of TNFa induce p75 expression, making olig0s more likely to undergo apoptosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32NS045468-02
Application #
6993580
Study Section
Special Emphasis Panel (ZRG1-F01 (20))
Program Officer
Kleitman, Naomi
Project Start
2004-12-01
Project End
2006-08-07
Budget Start
2005-12-01
Budget End
2006-08-07
Support Year
2
Fiscal Year
2006
Total Cost
$34,173
Indirect Cost
Name
Ohio State University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Ferguson, Adam R; Christensen, Randolph N; Gensel, John C et al. (2008) Cell death after spinal cord injury is exacerbated by rapid TNF alpha-induced trafficking of GluR2-lacking AMPARs to the plasma membrane. J Neurosci 28:11391-400
Christensen, Randolph N; Ha, Byeong Keun; Sun, Fang et al. (2006) Kainate induces rapid redistribution of the actin cytoskeleton in ameboid microglia. J Neurosci Res 84:170-81