TY - JOUR
T1 - Transient alterations of creatine, creatine phosphate, N-acetylaspartate and high-energy phosphates after mild traumatic brain injury in the rat.
AU - Signoretti, Stefano
AU - Di Pietro, Valentina
AU - Vagnozzi, Roberto
AU - Lazzarino, Giuseppe
AU - Amorini, Angela Maria
AU - Belli, Antonio
AU - D'Urso, Serafina
AU - Tavazzi, Barbara
PY - 2010
Y1 - 2010
N2 - 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" (1)H-magnetic resonance spectroscopy ((1)H-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 (1)H-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.
AB - 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" (1)H-magnetic resonance spectroscopy ((1)H-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 (1)H-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.
KW - N-acetylaspartate
KW - creatine
KW - creatine phosphate
KW - high-energy phosphates
KW - mild traumatic brain injury
KW - rat.
KW - N-acetylaspartate
KW - creatine
KW - creatine phosphate
KW - high-energy phosphates
KW - mild traumatic brain injury
KW - rat.
UR - http://hdl.handle.net/10807/6488
M3 - Article
SN - 0300-8177
VL - 2010
SP - 269
EP - 277
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
ER -