INHIBITION OF PHOSPHOLIPASE-C WITH NEOMYCIN IMPROVES METABOLIC AND NEUROLOGIC OUTCOME FOLLOWING TRAUMATIC BRAIN INJURY

Activation of phospholipase C has been implicated as a factor in the d evelopment of irreversible tissue damage following injury to the centr al nervous system. We have used phosphorus magnetic resonance spectros copy and a battery of postinjury motor function tests to characterize the role that phospholipase C activity may play in determining biochem ical and neurologic outcome following traumatic brain injury in rats. Moderate (2.7 atmospheres) fluid percussion induced lateral brain inju ry caused a decline in free magnesium concentration, phosphorylation p otential, and increased mitochondrial rate of oxidative phosphorylatio n. Neurologic motor score at 24 h and 1 week posttrauma in these anima ls was consistent with moderate injury. In contrast, treatment with th e phospholipase C inhibitor neomycin B (15 mg/kg i.v.) immediately pri or to injury significantly improved free magnesium status, bioenergeti c state and neurological outcome (P < 0.01) after injury. We propose t hat phospholipase C activated second messenger pathways affecting magn esium homeostasis are involved in determining outcome after brain inju ry.