The investigators propose first to define the role of MRS (spectroscopy) and MRI (imaging) in studies of surgically induced focal brain ischemia, and then to use both MRS and MRI as methods of studying vascular occlusive injuries, protection and therapy. Rodent and feline models with temporary and permanent regional brain ischemia will be studied using 31P and 1H NMR spectra and imaging, the latter to localize regions of interest for spectroscopic analysis and to qualitatively identify early and subtle ischemic alterations in configuration or distribution of brain water, blood, or lipids. Spectra will quantify ischemic alterations in lactate, ATP, creatine phosphate, inorganic phosphates, and intracellular pH permitting serial measurements of metabolic response immediately before, during, and after restoration of blood flow or other treatment of brain ischemia in the same animal during a single experiment. Treatments to be studied are hypothermia, relative hypoglycemia and hyperglycemia, lidocaine, mannitol, and fluosol-DA. NMR alterations will be correlated with alterations in EEG power spectra, neurological function, and brain histology. Groups of animals will be injected at the end of experiments with tracers to define distribution of local blood flow or cerebral glucose metabolic rate measured by autoradiography. In others, tissue samples will be subjected to HPLC for in vitro biochemical assay of membrane damage as indicated by phospholipids, free fatty acids, and arachidonic acid products, as well as indicators of lipid peroxidation. Enzymatic assay of energy metabolites will be performed to confirm MRS measurements. These procedures will be used to assess the variables controlling the magnitude of regional injury by MCAO, and to test therapeutic agents in rats and cats.
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