Inhibition of phospholipase C with neomycin improves metabolic and neurologic outcome following traumatic brain injury

Abstract

Activation of phospholipase C has been implicated as a factor in the development of irreversible tissue damage following injury to the central nervous system. We have used phosphorus magnetic resonance spectroscopy and a battery of postinjury motor function tests to characterize the role that phospholipase C activity may play in determining biochemical and neurologic outcome following traumatic brain injury in rats. Moderate (2.7 atmospheres) fluid percussion induced lateral brain injury caused a decline in free magnesium concentration, phosphorylation potential, and increased mitochondrial rate of oxidative phosphorylation. Neurologic motor score at 24 h and 1 week posttrauma in these animals was consistent with moderate injury. In contrast, treatment with the phospholipase C inhibitor neomycin B (15 mg/kg i.v.) immediately prior to injury significantly improved free magnesium status, bioenergetic state and neurological outcome (P < 0.01) after injury. We propose that phospholipase C activated second messenger pathways affecting magnesium homeostasis are involved in determining outcome after brain injury.