The specific aims of this project represent an attempt to quantitatively determine the inter-relationships among neuronal work, oxygen delivery and metabolism, and glucose delivery and metabolism in the rat brain during and after complete, reversible cerebral ischemia. Accomplishment of the aims will provide a basis for the description of the mechanisms which couple metabolism to function and how they are altered during and after stroke preventing full functional recovery. These goals will be reached through the use of reliable techniques and methodologies combining electrophysiological recording of brain activity, extracellular potassium and hydrogen ion activity, and tissue oxygen tension with optical monitoring of mitochondrial metabolism and intracellular pH by reflection spectrophotometry in situ under well controlled physiological and pathophysiological conditions. The data recorded from in vivo experiments will be compared directly with neurochemical correlates describing the metabolic state of the brain at significant times in the tissue response to stroke. The results from these proposed experiments will be directly applicable to the problem of brain dysfunction and recovery of function due to reversible or irreversible cell damage accompanying the imbalance between function and metabolism due to the pathophysiological stress which occurs during stroke. The uniqueness of this approach lies in the integration of various techniques which allow concurrent measurements of electrical brain activity, tissue oxygen content, cytochrome oxidase, potassium ion, hydrogen ion, and blood flow, volume and hemoglobin oxygenation; applied to the intact cerebral cortex in a manner which allows continuous determination in each rat during a variety of experimentally controlled conditions. This will allow specific analysis of the threat to continued normal brain function brought about by the failure of compensatory mechanisms which exist as a consequence of the total reliance of the brain on energy produced by oxygen metabolism.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS022077-02
Application #
3404017
Study Section
Neurology A Study Section (NEUA)
Project Start
1985-09-09
Project End
1988-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Kreisman, N R; LaManna, J C (1999) Rapid and slow swelling during hypoxia in the CA1 region of rat hippocampal slices. J Neurophysiol 82:320-9
Lauro, K L; Kabert, H; LaManna, J C (1999) Methyl isobutyl amiloride alters regional brain reperfusion after resuscitation from cardiac arrest in rats. Brain Res 831:64-71
Hoxworth, J M; Xu, K; Zhou, Y et al. (1999) Cerebral metabolic profile, selective neuron loss, and survival of acute and chronic hyperglycemic rats following cardiac arrest and resuscitation. Brain Res 821:467-79
LaManna, J C (1996) Hypoxia/ischemia and the pH paradox. Adv Exp Med Biol 388:283-92
Alcala, J R; Liao, S C; Zheng, J (1996) Real time frequency domain fibreoptic temperature sensor using ruby crystals. Med Eng Phys 18:51-6
Lin, C W; Kalaria, R N; Kroon, S N et al. (1996) The amiloride-sensitive Na+/H+ exchange antiporter and control of intracellular pH in hippocampal brain slices. Brain Res 731:108-13
Ferimer, H N; Kutina, K L; LaManna, J C (1995) Methyl isobutyl amiloride delays normalization of brain intracellular pH after cardiac arrest in rats. Crit Care Med 23:1106-11
LaManna, J C; Griffith, J K; Cordisco, B R et al. (1995) Rapid recovery of rat brain intracellular pH after cardiac arrest and resuscitation. Brain Res 687:175-81
Kreisman, N R; LaManna, J C; Liao, S C et al. (1995) Light transmittance as an index of cell volume in hippocampal slices: optical differences of interfaced and submerged positions. Brain Res 693:179-86
LaManna, J C; Harrington, J F; Vendel, L M et al. (1993) Regional blood-brain lactate influx. Brain Res 614:164-70

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