The proposed research will examine mechanisms of CNS white matter injury following anoxia- ischemia, which is of causal relevance to periventricular leukomalacia (PL), the most common neurological lesion associated with cerebral palsy. Whole white matter structures from perinatal rats will be subjected to anoxic-aglycemic insults in vitro under conditions that allow fluorescent imaging of intracellular free Ca and membrane integrity. Stated Aims are: to develop an appropriate model; to develop techniques for in situ measurements of Ca and membrane integrity; to use these methods to determine the responses to anoxic-aglycemic insults; to assess the importance of Ca influx versus release from intracellular stores; to assess the relative importance of voltage-gated Ca channels, ligand-gated Ca channels and Na/Ca exchange in mediating the observed changes; to assess the role of extracellular K and glutamate in these processes; and to apply the results of these experiments to the functional loss experienced by CNS white matter during anoxia-ischemia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29NS036790-03
Application #
2892324
Study Section
Special Emphasis Panel (ZRG1-NLS-3 (01))
Program Officer
Spinella, Giovanna M
Project Start
1997-08-01
Project End
2002-04-30
Budget Start
1999-05-01
Budget End
2000-04-30
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Washington
Department
Neurology
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195