Article

Molecular and Cellular Biochemistry

, Volume 333, Issue 1, pp 269-277

Transient alterations of creatine, creatine phosphate, N-acetylaspartate and high-energy phosphates after mild traumatic brain injury in the rat

  • Stefano SignorettiAffiliated withDivision of Neurosurgery, Department of Neurosciences-Head and Neck Surgery, “San Camillo” Hospital
  • , Valentina Di PietroAffiliated withInstitute of Biochemistry and Clinical Biochemistry, Catholic University of Rome
  • , Roberto VagnozziAffiliated withDepartment of Neurosciences, Chair of Neurosurgery, University of Rome “Tor Vergata”
  • , Giuseppe LazzarinoAffiliated withDivision of Biochemistry and Molecular Biology, Department of Chemical Sciences, University of CataniaDivision of Biochemistry and Molecular Biology, Department of Chemical Sciences, University of Catania Email author 
  • , Angela M. AmoriniAffiliated withInstitute of Biochemistry and Clinical Biochemistry, Catholic University of Rome
  • , Antonio BelliAffiliated withDivision of Clinical Neurosciences, University of Southampton
  • , Serafina D’UrsoAffiliated withDivision of Biochemistry and Molecular Biology, Department of Chemical Sciences, University of Catania
  • , Barbara TavazziAffiliated withInstitute of Biochemistry and Clinical Biochemistry, Catholic University of Rome

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Abstract

In this study, the concentrations of creatine (Cr), creatine phosphate (CrP), N-acetylaspartate (NAA), ATP, ADP and phosphatidylcholine (PC) were measured at different time intervals after mild traumatic brain injury (mTBI) in whole brain homogenates of rats. Anaesthetized animals underwent to the closed-head impact acceleration “weight-drop” model (450 g delivered from 1 m height = mild traumatic brain injury) and were killed at 2, 6, 24, 48 and 120 h after the insult (n = 6 for each time point). Sham-operated rats (n = 6) were used as controls. Compounds of interest were synchronously measured by HPLC in organic solvent deproteinized whole brain homogenates. A reversible decrease of all metabolites but PC was observed, with minimal values recorded at 24 h post-injury (minimum of CrP = 48 h after impact). In particular, Cr and NAA showed a decrease of 44.5 and 29.5%, respectively, at this time point. When measuring NAA in relation to other metabolites, as it is commonly carried out in “in vivo” 1H-magnetic resonance spectroscopy (1H-MRS), an increase in the NAA/Cr ratio and a decrease in the NAA/PC ratio was observed. Besides confirming a transient alteration of NAA homeostasis and ATP imbalance, our results clearly show significant changes in the cerebral concentration of Cr and CrP after mTBI. This suggests a careful use of the NAA/Cr ratio to measure NAA by 1H-MRS in conditions of altered cerebral energy metabolism. Viceversa, the NAA/PC ratio appears to be a better indicator of actual NAA levels during energy metabolism impairment. Furthermore, our data suggest that, under pathological conditions affecting the brain energetic, the Cr–CrP system is not a suitable tool to buffer possible ATP depletion in the brain, thus supporting the growing indications for alternative roles of cerebral Cr.

Keywords

Creatine Energy metabolism HPLC Magnetic resonance spectroscopy N-acetylaspartate Traumatic brain injury