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

  • Stefano Signoretti
  • Valentina Di Pietro
  • Roberto Vagnozzi
  • Giuseppe Lazzarino
  • Angela M. Amorini
  • Antonio Belli
  • Serafina D’Urso
  • Barbara Tavazzi
Article

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 

Abbreviations

Cho

Choline-containing compounds

Cr

Creatine

CK

Creatine kinase

CrP

Creatine phosphate

1H-MRS

1H-Magnetic resonance spectroscopy

mTBI

Mild traumatic brain injury

NAA

N-acetylaspartate

PC

Phosphatidylcholine

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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Stefano Signoretti
    • 1
  • Valentina Di Pietro
    • 2
  • Roberto Vagnozzi
    • 3
  • Giuseppe Lazzarino
    • 4
    • 6
  • Angela M. Amorini
    • 2
  • Antonio Belli
    • 5
  • Serafina D’Urso
    • 4
  • Barbara Tavazzi
    • 2
  1. 1.Division of Neurosurgery, Department of Neurosciences-Head and Neck Surgery“San Camillo” HospitalRomeItaly
  2. 2.Institute of Biochemistry and Clinical BiochemistryCatholic University of RomeRomeItaly
  3. 3.Department of Neurosciences, Chair of NeurosurgeryUniversity of Rome “Tor Vergata”RomeItaly
  4. 4.Division of Biochemistry and Molecular Biology, Department of Chemical SciencesUniversity of CataniaCataniaItaly
  5. 5.Division of Clinical NeurosciencesUniversity of SouthamptonSouthamptonUK
  6. 6.Division of Biochemistry and Molecular Biology, Department of Chemical SciencesUniversity of CataniaCataniaItaly

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