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

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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.

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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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Acknowledgements

This study has been supported by the research grant PRIN [2007JBHZ5F] of the Italian Ministry of University and Research (MIUR) and in part by research funds of Catholic University of Rome “Sacro Cuore” and University of Catania.

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Authors and Affiliations

  1. Division of Neurosurgery, Department of Neurosciences-Head and Neck Surgery, “San Camillo” Hospital, Rome, Italy

    Stefano Signoretti

  2. Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome, Rome, Italy

    Valentina Di Pietro, Angela M. Amorini & Barbara Tavazzi

  3. Department of Neurosciences, Chair of Neurosurgery, University of Rome “Tor Vergata”, Rome, Italy

    Roberto Vagnozzi

  4. Division of Biochemistry and Molecular Biology, Department of Chemical Sciences, University of Catania, Catania, Italy

    Giuseppe Lazzarino & Serafina D’Urso

  5. Division of Clinical Neurosciences, University of Southampton, Southampton, UK

    Antonio Belli

  6. Division of Biochemistry and Molecular Biology, Department of Chemical Sciences, University of Catania, Viale A. Doria 6, 95125, Catania, Italy

    Giuseppe Lazzarino

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  1. Stefano Signoretti
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  2. Valentina Di Pietro
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Correspondence to Giuseppe Lazzarino.

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Signoretti, S., Di Pietro, V., Vagnozzi, R. et al. Transient alterations of creatine, creatine phosphate, N-acetylaspartate and high-energy phosphates after mild traumatic brain injury in the rat. Mol Cell Biochem 333, 269–277 (2010). https://doi.org/10.1007/s11010-009-0228-9

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