title: Persistent metabolic sequelae of severe head injury in humans in vivo.
abstract: Six patients who had suffered severe non-penetrating high velocity head injuries were investigated with phosphorus (31P) magnetic resonance spectroscopy (MRS) to determine, non-invasively, long-term alteration in intracellular biochemistry. The normal subjects were found to have a constant intracellular pH (pHi, 7.03 +/- 0.03) with depth into the brain. The adenosine triphosphate (ATP, 3.46 +/- 0.66 mmol/L of brain tissue), inorganic phosphate (Pi, 1.15 +/- 0.41 mmol/L) and phosphomonester (PME, 2.76 +/- 1.0 mmol/L) tissue concentrations did not alter significantly with depth into normal brain. The phosphocreatine (PCr, 2 cm = 5.21 +/- 1.25, 5 cm = 4.85 +/- 1.49 mmol/L) was slightly reduced, whilst phosphodiesters (PDE, 2 cm = 9.53 +/- 2.6, 5 cm = 14.41 +/- 4.2 mmol/L) rose significantly between tissue comprising mainly of gray (2 cm) and white matter (5 cm). In comparison the contra-lateral hemisphere to the side of worst spasticity showed significant changes a considerable time after injury (6-18 months). The intracellular metabolite tissue concentrations were all reduced by 30% (ATP 2.53 +/- 1.0 mmol/L, PCr 3.44 +/- 0.8 mmol/L) with PDE reduced most significantly at depth (5 cm = 8.4 +/- 3.4 mmol/L), compatible with the cerebral atrophy seen in these patients. In white matter the pHi also decreased with depth (2 cm = 7.03 +/- 0.03, 5 cm = 6.89 +/- 0.05). The reduction in pHi so long after injury is difficult to explain in these steady-state conditions. A structural abnormality, such as a disorder in the blood brain barrier or accumulation of large acidic lysosomes, could cause these pHi changes. There may also be a failure in blood flow regulation, with near critical fluctuations in blood flow both with time and space.
authors.affiliation: M.R.C. Clinical and Biochemical Magnetic Resonance Unit, John Radcliffe Hospital, Oxford.
authors.forename: T A
authors.initials: TA
authors.lastname: Cadoux-Hudson
authors.forename: D
authors.initials: D
authors.lastname: Wade
authors.forename: D J
authors.initials: DJ
authors.lastname: Taylor
authors.forename: B
authors.initials: B
authors.lastname: Rajagopalan
authors.forename: J G
authors.initials: JG
authors.lastname: Ledingham
authors.forename: M
authors.initials: M
authors.lastname: Briggs
authors.forename: G K
authors.initials: GK
authors.lastname: Radda
mesh_terms: D000063:Accidents, Traffic; D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D007839:Functional Laterality; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D009943:Organophosphorus Compounds / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D010758:Phosphorus; D012016:Reference Values; D014950:Wounds, Penetrating
chemical_list: D009943:Organophosphorus Compounds; D010710:Phosphates; D010725:Phosphocreatine; D010758:Phosphorus; D000255:Adenosine Triphosphate