title: 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.
authors.affiliation: Division of Biochemistry and Human Physiology, James Cook University of North Queensland, Townsville, Australia.
authors.forename: E M
authors.initials: EM
authors.lastname: Golding
authors.forename: R
authors.initials: R
authors.lastname: Vink
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D005601:Framycetin / Q000494:pharmacology*; D008274:Magnesium / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D010758:Phosphorus; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D010758:Phosphorus; D005601:Framycetin; D010738:Type C Phospholipases; D008274:Magnesium