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

Transient alterations of creatine, creatine phosphate, N-acetylaspartate and high-energy phosphates after mild traumatic brain injury in the rat.
Transient alterations of creatine, creatine phosphate, N-acetylaspartate and high-energy phosphates after mild traumatic brain injury in the rat.
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
creatine, energy metabolism, HPLC, magnetic resonance, spectroscopy, N-acetylaspartate, Traumatic brain injury
0300-8177
269-277
Signoretti, Stefano
55ae0833-9e5f-410a-ad3c-25f7dec233f5
Di Pietro, Valentina
52a26fb6-7579-4cdc-aee6-26cb6e9ff175
Vagnozzi, Roberto
3c1c46f7-9a64-459e-82cd-50cf9ee73a2e
Lazzarino, Giuseppe
2344efe0-43bc-4781-9f72-451f3d7f407d
Amorini, Angela M.
36f27349-dfe1-47db-af7d-4437a6f4f8ee
Belli, Antonio
33707b7b-b004-4245-aead-98a8e1e2b2e2
D'Urso, Serafina
30951fc2-bcf5-4c99-b4f7-2a7f040ac899
Tavazzi, Barbara
22416dea-27d4-496d-8104-803bc0b0f13c
Signoretti, Stefano
55ae0833-9e5f-410a-ad3c-25f7dec233f5
Di Pietro, Valentina
52a26fb6-7579-4cdc-aee6-26cb6e9ff175
Vagnozzi, Roberto
3c1c46f7-9a64-459e-82cd-50cf9ee73a2e
Lazzarino, Giuseppe
2344efe0-43bc-4781-9f72-451f3d7f407d
Amorini, Angela M.
36f27349-dfe1-47db-af7d-4437a6f4f8ee
Belli, Antonio
33707b7b-b004-4245-aead-98a8e1e2b2e2
D'Urso, Serafina
30951fc2-bcf5-4c99-b4f7-2a7f040ac899
Tavazzi, Barbara
22416dea-27d4-496d-8104-803bc0b0f13c

Signoretti, Stefano, Di Pietro, Valentina, Vagnozzi, Roberto, Lazzarino, Giuseppe, Amorini, Angela M., Belli, Antonio, D'Urso, Serafina and Tavazzi, Barbara (2009) Transient alterations of creatine, creatine phosphate, N-acetylaspartate and high-energy phosphates after mild traumatic brain injury in the rat. Molecular and Cellular Biochemistry, 333 (1-2), 269-277. (doi:10.1007/s11010-009-0228-9).

Record type: 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

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Published date: 18 August 2009
Keywords: creatine, energy metabolism, HPLC, magnetic resonance, spectroscopy, N-acetylaspartate, Traumatic brain injury

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Local EPrints ID: 141995
URI: http://eprints.soton.ac.uk/id/eprint/141995
ISSN: 0300-8177
PURE UUID: 84408782-17cd-4e85-99b6-42eed63cd8a0

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Date deposited: 30 Mar 2010 11:17
Last modified: 14 Mar 2024 00:38

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Contributors

Author: Stefano Signoretti
Author: Valentina Di Pietro
Author: Roberto Vagnozzi
Author: Giuseppe Lazzarino
Author: Angela M. Amorini
Author: Antonio Belli
Author: Serafina D'Urso
Author: Barbara Tavazzi

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