| Objective: The effect and function of adenosine had been generously reported in various cerebral ischemia models.But it had been seldomly reported in brain injury model. The aim of the study was to evaluate cerebral extracell glucose (Glu),lactic acid (Lac),pyruvic acid(Pyru) and glycerol(Gly) in the contralateral hippocampus and effects of adenosine,adenosine analogue (2-chloroadenosine) and adenosine kinase inhibitor (Abt-702) following traumatic brain injury in rats using in vivo microdialysis,discuss the effect of adenosine in secondary brain injury mechanisms, explore secondary brain injury mechanisms and evaluate new therapies for the treatment of traumatic brain injury.Methods:forty-eight adult male Sprague-Dawley rats were used in the experiments. Rats were randomly allocated among five groups. Animals were anesthetized with 10% chloral hydrate(0. 35g/kg i.p). The trauma was induced by the fluid percussion device. Rats were injured at a moderate magnitude of injury (152. 0±20. 3 kPa). A 3mm bore hole was done at contralateral hippocampus. One microdialysis probe was implanted in the right parietal cortex. Dialysate perfusion was performed with artificial cerebrospinal fluid at a flow rate of 4.0μl/min. 1 cube of cerebral extracell fluid for microdialysis was obtained every 0. 5h from contralateral hippocampus after Fluid Percussion TBI. In adenosine and 2-chloroadenosine groups, cisterna magna were puncted after fluid percussion TBI. Adenosine(1000μmol/L) and 2-chloroadenosine (500μmol/L) were individually perfused 30 min after injury at a rate of 2μl/min using a microsyring pump persisting 3h. In Abt-702 group, Abt-702 was administered i.p. to mice 30 rain after injury (8μmol/kgdissolved in DMSO). Sampling of the dialysate was performed for 5h. Analyses of Glu,Lac, pyru and Gly were performed with a CMA600 analyzer. Data are expressed as mean±standard error of the mean Microdialysate data were analyzed with a repeated-measures analysis of variance for differences between time points and groups, followed by Fisher's post hocttest. Significance was set at a value of P<0. 05. Results: In normal group, brain extracellular fluid Glu, Lac, Pyru and Gly remained at a stabilized level 2 hour after Dialysate perfusion. In fluid percussion injury group, Glu concentration had significantly decreased to 630±65μmol/l at 2 hours after injury (P<0. 05) and was significantly lower (710±25μmol /l) than in the other three treated groups at 4 hours after injury as well as before in jury (P<0. 05). Brain extracellular fluid lactate increased to 960±68μmol/L at 1. 5 hours after injury (P<0. 05) and was significantly higher (780±38μmol/L) than in the other three treated groups at 4 hours after injury as well as before injury (P<0. 05). The concentration of Pyru mountained at a level of 31. 2±5. 3μmol/l to 33. 5±4. 3μmol/l. The concentration of Gly also remained at a stable level of 41. 1±3. 5μmol/l (P>0. 05). The Lac Pyru ratio increased to 25. 1±3. 5. In adenosine group, Lac increased to 760±45μmol/L at 3 hours after injury (P<0. 05) and then gradually decreased to 450±72μmol/L at 5 hours after injury. Glu decreased to 740±36μmol/l at 3 hours after injury (P<0. 05) and gradually increased to 940±72μmol/L at 5 hours. In 2-chloroadenosine group, Glu decreased to 710±58μmol/l at 2 hours after injury(P<0. 05) and gradually increased to 930±42μmol/L at 5 hours. Lac increased to 680±48μmol/L at 2 hours after injury (P< 0.05) and then gradually decreased to 423±58μmol/L at 5 hours after injury. Conclusion: Our data from this study showed that disturbances in energetic metabolism had been found in relatively normal tissues after brain trauma at early time points after TBI.Exogenous adenosine, endogenous adenosine and adenosine analogue could improve blood supply, reduce anaerobic glycolysis, amend energetic metabolism. |
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