Cerebral oxidative stress and depression of energy metabolism correlate with severity of diffuse brain injury in rats.
OBJECTIVE
The combined effect of traumatic brain injury (TBI) and secondary insult on biochemical changes of cerebral tissue is not well known. For this purpose, we studied the time-course changes of parameters reflecting ROS-mediated oxidative stress and modifications of cell energy metabolism determined in rats subjected to cerebral insult of increasing severity.


METHODS
Rats were divided into four groups: 1) sham-operated, 2) subjected to 10 minutes of hypoxia and hypotension (HH), 3) subjected to severe diffuse TBI, and 4) subjected to severe diffuse TBI + HH. Rats were killed at different times after injury, and analyses of malondialdehyde, ascorbate, high-energy phosphates, nicotinic coenzymes, oxypurines, nucleosides, and N-acetylaspartate (NAA) were made by high-performance liquid chromatography on whole-brain tissue extracts.


RESULTS
Data indicated a close relationship between degree of oxidative stress and severity of brain insult, as evidenced by the highest malondialdehyde values and lowest ascorbate levels in rats subjected to TBI + HH. Similarly, modifications of parameters related to cell energy metabolism were modulated by increasing severity of brain injury, as demonstrated by the lowest values of energy charge potential, nicotinic coenzymes, and NAA and the highest levels of oxypurines and nucleosides recorded in TBI + HH rats. Both the intensity of oxidative stress-mediated cerebral damage and perturbation of energy metabolism were minimally affected in rats subjected to HH only.


CONCLUSIONS
These results showed that the severity of brain insult can be graded by measuring biochemical modifications, specifically, reactive oxygen species-mediated damage, energy metabolism depression, and NAA, thereby validating the rodent model of closed-head diffuse TBI coupled with HH and proposing NAA as a marker with diagnostic relevance to monitor the metabolic state of postinjured brain.
Tavazzi
Barbara
B
Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome, Rome, Italy.
Signoretti
Stefano
S
Lazzarino
Giuseppe
G
Amorini
Angela M
AM
Delfini
Roberto
R
Cimatti
Marco
M
Marmarou
Anthony
A
Vagnozzi
Roberto
R
D000818:Animals; D001205:Ascorbic Acid / Q000032:analysis; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D001930:Brain Injuries / Q000145:classification / Q000209:etiology / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004734:Energy Metabolism; D016489:Head Injuries, Closed / Q000150:complications; D007022:Hypotension / Q000150:complications / Q000378:metabolism; D000860:Hypoxia / Q000150:complications / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D009243:NAD / Q000032:analysis; D009249:NADP / Q000032:analysis; D009705:Nucleosides / Q000032:analysis; D018384:Oxidative Stress; D010710:Phosphates / Q000032:analysis; D011687:Purines / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000032:analysis
D015415:Biomarkers; D009705:Nucleosides; D010710:Phosphates; D011687:Purines; D017382:Reactive Oxygen Species; D009243:NAD; D001224:Aspartic Acid; D008315:Malondialdehyde; D009249:NADP; C000179:N-acetylaspartate; D001205:Ascorbic Acid