Utilizing an isolated brain preparation under control conditions, we have demonstrated the presence of six compartments in the NMR Pi spectrum of normal brain, two extracellular and four intracellular. With in vivo NMR, the Pi-containing intracellular compartments can be identified indirectly by processes designed to selectively affect physical and metabolic changes in the Pi, pHi or phosphorylated sugar content of a specific compartment or related group of compartments. 2-Deoxyglucose (2-DG) is taken up by the four intracellular compartments and can be used to track intracellular peaks during ischemia and assess intracellular glucose utilization under experimental conditions. We propose to establish the identity of the four intracellular compartments and study the global ATP turnover and intracellular glucose (2-DG) uptake by the compartments under physiologic conditions (high and low cerebral blood flow, hypoxia, hypo-and hyperglycemia, hypo-and hypercapnia, hypo-and hyperthermia) and experimental conditions (seizures, anesthesia, ammonia infusion, hypoxia and ischemia). Linking the 31Pi peaks and glucose utilization to specific cell types in normal and experimental brains opens the future possibility of monitoring the metabolic response of each brain cell type in vivo. The proposed studies have the promise of providing the first quantitative information relating control conditions to energy metabolism, pHi, cellular vulnerability and irreversible brain damage under pathologic conditions such as hypoxia and ischemia. These data could serve as a basis for therapeutic measures aimed at correcting disorders in specific types of brain cells.
| Kintner, D B; Anderson, M K; Fitzpatrick Jr, J H et al. (2000) 31P-MRS-based determination of brain intracellular and interstitial pH: its application to in vivo H+ compartmentation and cellular regulation during hypoxic/ischemic conditions. Neurochem Res 25:1385-96 |
| Kintner, D B; Fitzpatrick Jr, J H; Gilboe, D D (1997) Hyperglycemic damage to mitochondrial membranes during cerebral ischemia: amelioration by platelet-activating factor antagonist BN 50739. J Neurochem 69:1219-27 |
