High Energy Phosphate Metabolism in Experimental Permanent Focal Cerebral Ischemia: An in vivo31P Magnetic Resonance Spectroscopy Study

Abstract

Relative levels of phosphate metabolites in the brain were examined in vivo by31P magnetic resonance spectroscopy (MRS) in 50 Sprague-Dawley rats before, during, and after induction of focal permanent cerebral ischemia. After acquisition of baseline spectra, rats were subjected to injury within the core of the MR spectrometer, and31P spectra were collected for 60 min after injury: in 7 rats, permanent, acute focal cerebral ischemia was induced (ischemia group); in 6 rats, mild hypoxia (FiO214%) was induced at the time of the ischemic insult and was maintained for 20 min (ischemia-hypoxia group); in 6 rats, mild hypoxia (FiO214%) only was induced for 20 min (hypoxia group). Control studies were performed in 25 rats. Cerebral intracellular pH, calculated from the chemical shift of inorganic phosphate (Pi), decreased immediately after injury in the ischemia and ischemia-hypoxia groups. The first31P spectrum obtained after injury was characterized by an increase in Pi and a decrease in phosphocreatine (PCr) in the ischemia and ischemia-hypoxia groups; these changes in spectra were significantly greater in the ischemia-hypoxia group. No significant changes in adenosine triphosphate (ATP) were found in either group. Within 60 min of occlusion,31P spectra returned toward baseline spectra in both ischemia-hypoxia and ischemia groups. No significant changes were seen in spectra of rats subjected to hypoxia alone. These results confirm that31P MRS is a sensitive measure of early changes of high energy metabolites in focal cerebral ischemia. The return of spectra toward baseline values within 1 h of injury despite the presence of permanent ischemic damage, however, suggests that caution should be used in attempts to interpret “recovery” of31P MRS.