Changes in Cellular Bioenergetic State Following Graded Traumatic Brain Injury in Rats: Determination by Phosphorus 31 Magnetic Resonance Spectroscopy

Abstract

Phosphorus 31 magnetic resonance spectroscopy (³¹P MRS) was used to study noninvasively the intracellular free Mg²⁺ concentration and cellular bioenergetic state of rat brain in vivo before and after fluid percussion-induced traumatic brain injury of graded severity. Brain injury was induced at four levels: low (1.0 ± 0.5 atm); moderate (2.1 ± 0.4 atm); high (3.9 ± 0.9 atm); and severe (5.9 ± 0.7 atm). Prior to injury, mean intracellular values for all groups (n = 24; mean ± SE) were as follows: pH = 7.11 ± 0.03; free [Mg²⁺] = 0.99 ± 0.07 mM; cytosolic [ADP] = 25.2 ± 0.8 nmol/g wet weight; cytosolic [AMP] = 0.29 ± 0.02 nmol/g wet weight; cytosolic phosphorylation potential = 118.5 ± 3.1 × 10³ M⁻¹; free energy of ATP hydrolysis = 62.11 ± 0.04 kJ/mole; and energy charge = 0.99 ± 0.01. Following every level of injury, there were decreases in intracellular free Mg²⁺ concentration, and alterations in the intracellular pH. These posttraumatic changes in Mg²⁺ and pH induced shifts in the equilibrium constants of the creatine kinase, adenylate kinase, and ATPase reactions, resulting in alterations in [ADP], [AMP], cytosolic phosphorylation potential, and free energy of hydrolysis, but not in the energy charge. The alterations in cytosolic phosphorylation potential following trauma were linearly correlated with the changes in intracellular free Mg²⁺ concentration. None of the individual bioenergetic parameters could be correlated with the severity of injury over the entire injury range; however, an association between cytosolic phosphorylation potential and reversibility of injury was apparent. These results suggest that reductions in cellular bioenergetic state following traumatic brain injury occur through a posttraumatic decrease in the cells' capacity for oxidative phosphorylation, which itself may be directly related to the intracellular free Mg²⁺ concentration.