The specific aim of this study is to clarify the relationship between post ischemic brain tissue alkalosis and ischemic neuronal damage, and ultimately to demonstrate that brain alkalosis, as measured by NMR, is a useful marker of neuronal injury. The following Specific Aims are in accord with this goal: 1) To measure brain pH, using in vivo 31P phosphorous NMR spectroscopy serially for one week following the induction of ischemia, and to also measure neuronal damage in the same tissue. These measurements will be performed as a function of the duration of transient forebrain ischemia, as well as for a """"""""protective"""""""" hypothermic intervention in the rat. The hypothesis being tested is that the extent of neuronal cell damage is directly correlated with the magnitude, onset time and duration of alkalosis detected from the same tissue. The basis for this correlation is that the temporal profile of alkalosis reflects cellular inflammatory processes, associated with neuronal damage. 2) To measure, at particular time points after ischemia, inflammatory cellular response and glial proliferation, neuronal damage and brain tissue pH, as a function of the duration of transient forebrain ischemia and for a hypothermic intervention. The hypothesis being tested is that inflammatory cellular response and glial proliferation is directly correlated to neuronal damage; hence brain tissue alkalosis is directly correlated to neuronal damage. 3) To measure, in conjunction with the above studies, cerebral blood flow and relative concentrations of brain high energy phosphates and lactates. These measurements will address the relationship between brain tissue alkalosis, and CBF and metabolic changes in the tissue. It is proposed that post ischemic brain pH changes will be closely coupled to ultimate tissue viability, and that the studies will therefore highlight the potential diagnostic significance of chronic pH measurements in stroke patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS029463-04
Application #
2267630
Study Section
Neurology A Study Section (NEUA)
Project Start
1991-05-01
Project End
1995-04-30
Budget Start
1994-05-01
Budget End
1995-04-30
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Henry Ford Health System
Department
Neurology
Type
Schools of Medicine
DUNS #
073134603
City
Detroit
State
MI
Country
United States
Zip Code
48202
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Jiang, N; Finklestein, S P; Do, T et al. (1996) Delayed intravenous administration of basic fibroblast growth factor (bFGF) reduces infarct volume in a model of focal cerebral ischemia/reperfusion in the rat. J Neurol Sci 139:173-9
Li, Y; Chopp, M; Jiang, N et al. (1995) In situ detection of DNA fragmentation after focal cerebral ischemia in mice. Brain Res Mol Brain Res 28:164-8
Kim, J S; Chopp, M; Chen, H et al. (1995) Adhesive glycoproteins CD11a and CD18 are upregulated in the leukocytes from patients with ischemic stroke and transient ischemic attacks. J Neurol Sci 128:45-50
Zhang, R L; Chopp, M; Jiang, N et al. (1995) Anti-intercellular adhesion molecule-1 antibody reduces ischemic cell damage after transient but not permanent middle cerebral artery occlusion in the Wistar rat. Stroke 26:1438-42;discussion 1443
Li, Y; Sharov, V G; Jiang, N et al. (1995) Ultrastructural and light microscopic evidence of apoptosis after middle cerebral artery occlusion in the rat. Am J Pathol 146:1045-51
Zhang, R L; Chopp, M; Zaloga, C et al. (1995) The temporal profiles of ICAM-1 protein and mRNA expression after transient MCA occlusion in the rat. Brain Res 682:182-8
Li, Y; Chopp, M; Jiang, N et al. (1995) Induction of DNA fragmentation after 10 to 120 minutes of focal cerebral ischemia in rats. Stroke 26:1252-7;discussion 1257-8
Li, Y; Chopp, M; Zhang, Z G et al. (1995) Expression of glial fibrillary acidic protein in areas of focal cerebral ischemia accompanies neuronal expression of 72-kDa heat shock protein. J Neurol Sci 128:134-42
Hurd, K; Chopp, M; Vande Linde, A M et al. (1995) Effects of moderate hyperglycemia on the temporal profile of brain tissue intracellular pH and [Mg2+] after global cerebral ischemia in rats. J Neurol Sci 129:90-6

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