Abstract

The goal of this project for the coming year is to continue our studies of the mechanisms underlying the responses of the central nervous system (CNS) to injury and the basis for the partial recovery that can occur with time. Animal models of CNS lesions affecting adult humans will be created in mature animals with ablations of the cerebral cortex and with kainic acid and 6-hydroxydopamine induced lesions of the basal ganglia and thalamus. Animal models of CNS injury affecting immature humans will be produced in neonatal animals with ablations of the cerebral cortex and with cerebral lesions induced by hypoxic-ischemic insults. A central focus concerns the immediate and long-term responses to injury of CNS neurotransmitter receptor systems including glutamate, Gamma-aminobutyric acid/benzodiazepine, opiates, dopamine, and acetylcholine. Investigations will be performed using awake behaving animals, tissue from basal ganglia, thalamus, brainstem and spinal cord, and neuronal cell cultures. The experimental approaches include recordings of single neuronal unit activity, studies of neurotransmitter receptors, determinations of glucose metabolic activity, and investigation of ionic conductances in mammalian nerve cell membranes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS019613-04
Application #
3099778
Study Section
(SRC)
Project Start
1984-12-01
Project End
1989-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109

  Publications

Deng, Y P; Albin, R L; Penney, J B et al. (2004) Differential loss of striatal projection systems in Huntington's disease: a quantitative immunohistochemical study. J Chem Neuroanat 27:143-64
Greenfield Jr, L John; Zaman, Shahid H; Sutherland, Margaret L et al. (2002) Mutation of the GABAA receptor M1 transmembrane proline increases GABA affinity and reduces barbiturate enhancement. Neuropharmacology 42:502-21
Greene, J G; Sheu, S S; Gross, R A et al. (1998) 3-Nitropropionic acid exacerbates N-methyl-D-aspartate toxicity in striatal culture by multiple mechanisms. Neuroscience 84:503-10
Wullner, U; Standaert, D G; Testa, C M et al. (1997) Differential expression of kainate receptors in the basal ganglia of the developing and adult rat brain. Brain Res 768:215-23
Aldridge, J W; Thompson, J F; Gilman, S (1997) Unilateral striatal lesions in the cat disrupt well-learned motor plans in a GO/NO-GO reaching task. Exp Brain Res 113:379-93
Gross, R A; Covey, D F; Ferrendelli, J A (1997) Voltage-dependent calcium channels as targets for convulsant and anticonvulsant alkyl-substituted thiobutyrolactones. J Pharmacol Exp Ther 280:686-94
Kume, A; Greenfield Jr, L J; Macdonald, R L et al. (1996) Felbamate inhibits [3H]t-butylbicycloorthobenzoate (TBOB) binding and enhances Cl- current at the gamma-aminobutyric AcidA (GABAA) receptor. J Pharmacol Exp Ther 277:1784-92
Kaatz, K W; Albin, R L (1996) Intraseptal administration of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid induces immediate early gene expression in lateral septal neurons. Brain Res 709:205-14
Milbrandt, J C; Albin, R L; Turgeon, S M et al. (1996) GABAA receptor binding in the aging rat inferior colliculus. Neuroscience 73:449-58
Penney, J B; Standaert, D G; Testa, C M et al. (1996) Glutamate receptor genes in Parkinson's disease. Adv Neurol 69:79-86

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