title: Dissociation of adenosine levels from bioenergetic state in experimental brain trauma: potential role in secondary injury.
abstract: Intracellular bioenergetic state and extracellular adenosine levels were monitored in rat brain prior to and following traumatic brain injury (TBI) using phosphorus magnetic resonance spectroscopy and microdialysis, respectively. Fluid percussion-induced TBI (2.6 +/- 0.2 atm) resulted in significant reductions in free cytosolic [Mg2+], cytosolic [ATP]/[ADP] [P(i)], and delta GATP and elevations in cytosolic [ADP] and [5'-AMP]. Intracellular ATP concentration and pH did not change significantly after trauma. Mitochondrial capacity for oxidative phosphorylation (indexed by V/Vmax) increased significantly from approximately 0.45 prior to injury to approximately 0.58 following TBI. All metabolic changes were maximal at 2-3 h post-TBI. Conversely, extracellular adenosine concentrations increased transiently following TBI, with levels peaking at 10 min posttrauma, then declining rapidly to preinjury values by 50 min. Thus, despite pronounced long-term depression in bioenergetic status and a marked rise in [5'-AMP], formation and release of adenosine were elevated only transiently within the first hour following TBI. Since steady-state adenosine levels were essentially unchanged beyond 1 h posttrauma, mooted neuroprotective actions of endogenous adenosine would be minimized. Intracerebroventricular injections of 2-chloroadenosine (0.5 and 2.5 nmol) immediately prior to TBI dose-dependently attenuated metabolic disturbances and improved posttraumatic neurologic outcome (p < 0.05). The observations indicate that (a) TBI results in dissociation of adenosine release from intracellular bioenergetic state, a phenomenon possibly contributing to secondary injury following TBI; and (b) supplementing brain with an adenosine agonist attenuates irreversible injury.
authors.affiliation: Department of Molecular Sciences, James Cook University of North Queensland, Townsville, Australia.
authors.forename: J P
authors.initials: JP
authors.lastname: Headrick
authors.forename: M R
authors.initials: MR
authors.lastname: Bendall
authors.forename: A I
authors.initials: AI
authors.lastname: Faden
authors.forename: R
authors.initials: R
authors.lastname: Vink
mesh_terms: D015762:2-Chloroadenosine / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001930:Brain Injuries / Q000378:metabolism* / Q000503:physiopathology; D004734:Energy Metabolism; D007700:Kinetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D015762:2-Chloroadenosine; D000241:Adenosine