Oxidative Stress in Brain According to Traumatic Brain Injury Intensity (original) (raw)
Related papers
Oxidative Stress Following Traumatic Brain Injury in Rats
Journal of Neurochemistry, 2002
Oxidative stress may contribute to many pathophysiologic changes that occur after traumatic brain injury. In the current study, contemporary methods of detecting oxidative stress were used in a rodent model of traumatic brain injury. The level of the stable product derived from peroxidation of arachidonyl residues in phospholipids, 8-epi-prostaglandin F 2␣ , was increased at 6 and 24 h after traumatic brain injury. Furthermore, relative amounts of fluorescent end products of lipid peroxidation in brain extracts were increased at 6 and 24 h after trauma compared with sham-operated controls. The total antioxidant reserves of brain homogenates and water-soluble antioxidant reserves as well as tissue concentrations of ascorbate, GSH, and protein sulfhydryls were reduced after traumatic brain injury. A selective inhibitor of cyclooxygenase-2, SC 58125, prevented depletion of ascorbate and thiols, the two major water-soluble antioxidants in traumatized brain. Electron paramagnetic resonance (EPR) spectroscopy of rat cortex homogenates failed to detect any radical adducts with a spin trap, 5,5-dimethyl-1-pyrroline N-oxide, but did detect ascorbate radical signals. The ascorbate radical EPR signals increased in brain homogenates derived from traumatized brain samples compared with sham-operated controls. These results along with detailed model experiments in vitro indicate that ascorbate is a major antioxidant in brain and that the EPR assay of ascorbate radicals may be used to monitor production of free radicals in brain tissue after traumatic brain injury.
Traumatic Brain Injury: Oxidative Stress and Neuroprotection
Antioxidants & Redox Signaling, 2013
Significance: A vast amount of circumstantial evidence implicates high energy oxidants and oxidative stress as mediators of secondary damage associated with traumatic brain injury. The excessive production of reactive oxygen species due to excitotoxicity and exhaustion of the endogenous antioxidant system induces peroxidation of cellular and vascular structures, protein oxidation, cleavage of DNA, and inhibition of the mitochondrial electron transport chain. Recent Advances: Different integrated responses exist in the brain to detect oxidative stress, which is controlled by several genes termed vitagens. Vitagens encode for cytoprotective heat shock proteins, and thioredoxin and sirtuins. Critical Issues and Future Directions: This article discusses selected aspects of secondary brain injury after trauma and outlines key mechanisms associated with toxicity, oxidative stress, inflammation, and necrosis. Finally, this review discusses the role of different oxidants and presents potential clinically relevant molecular targets that could be harnessed to treat secondary injury associated with brain trauma. Antioxid. Redox Signal.
Early oxidative status in adult patients with isolated traumatic brain injury
Turkish Journal of Medical Sciences
To investigate oxidative and antioxidative status, as well as the Glasgow Coma Scale (GCS) and Revised Trauma Score (RTS), refl ecting injury severity and neurological outcome during the early posttraumatic period in patients with isolated traumatic brain injury (TBI). Materials and methods: Fift y-one adult patients with TBI and 45 eligible healthy volunteers as control subjects were enrolled. Plasma total oxidant status (TOS), total antioxidant status (TAS), and the oxidative stress index (OSI) were calculated as biomarkers of early oxidative changes in serum using a novel automated method. Results: TOS levels and OSI values were signifi cantly higher in nonsurvivors compared with those in survivors. However, there was no signifi cant diff erence in TAS levels between survivors and nonsurvivors. GCS and RTS showed negative correlations with TOS levels, but neither was signifi cantly related to OSI levels. Furthermore, GCS scores were negatively correlated with TAS levels, whereas RTS scores were not signifi cantly related to TAS levels. Conclusion: Patients with isolated TBI are exposed to potent oxidative stress. TOS, as an early oxidative stress biomarker, might refl ect the severity of cerebral insult in those patients.
Oxidative stress in isolated blunt traumatic brain injury
Scientific Research and Essays, 2010
Traumatic brain injury is a common cause of death after trauma. The aim of this study was to investigate the relationship between oxidative stress parameters and, outcomes and clinical findings in patients with isolated traumatic brain injuries. Fifty-four patients who were admitted into the emergency department of Ankara Ataturk Training and Research hospital with isolated blunt traumatic brain injuries and 33 healthy adults as control group, were included in this study. Serum oxidant status was evaluated by measuring Total Oxidant Status (TOS) levels in patients with traumatic brain injury and in healthy individuals. Serum antioxidant status was evaluated by measuring Total Antioxidant Status (TAS) levels. Then, also Oxidative Stress Index (OSI) was calculated. A total of 54 patients with isolated traumatic brain injuries (mean age 36.7 ± 18.3 years; 60.4% male, 39.6% female) were enrolled. TOS and OSI levels increased in patient group compared to the control group. High levels of OSI, TOS and TAS were observed in patients who finally became dead. A significant correlation between symptoms including nausea, vomitus, loss of consciousness, seizing and TOS, OSI levels of all patients have been observed. Moreover, there was a meaningful correlation between Glaskow Coma Scale (GCS) score, TOS and OSI levels of patients. The oxidative stress parameters may be valuable prognostic markers in traumatic brain injury patients. It can be concluded that oxidative stress parameters may be valuable in the assessment of clinical severity and in predicting outcome of traumatic brain injury patients.
Neurosurgery, 2005
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 ϩ 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 highperformance 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 ϩ 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 ϩ 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. CONCLUSION: 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.
BioMed Research International, 2014
The oxidative stress is believed to be one of the mechanisms involved in the neuronal damage after acute traumatic brain injury (TBI). However, the disease severity correlation between oxidative stress biomarker level and deep brain microstructural changes in acute TBI remains unknown. In present study, twenty-four patients with acute TBI and 24 healthy volunteers underwent DTI. The peripheral blood oxidative biomarkers, like serum thiol and thiobarbituric acid-reactive substances (TBARS) concentrations, were also obtained. The DTI metrics of the deep brain regions, as well as the fractional anisotropy (FA) and apparent diffusion coefficient, were measured and correlated with disease severity, serum thiol, and TBARS levels. We found that patients with TBI displayed lower FAs in deep brain regions with abundant WMs and further correlated with increased serum TBARS level. Our study has shown a level of anatomic detail to the relationship between white matter (WM) damage and increased ...
Journal of Cerebral Blood Flow & Metabolism, 1997
It has been suggested that reactive oxygen species (ROS) play a role in the pathophysiology of brain damage, A number of therapeutic approaches, based on scavenging these radicals, have been attempted both in experimental models and in the clinical setting, In an experimental rat and mouse model of closed-head injury (CHI), we have studied the total tissue nonenzymatic antioxidant capacity to combat ROS, A major mechanism for neutralizing ROS uses endogenous low molecular weight antioxidants (LMW A), This review deals with the source i\ild nature of ROS in the brain, along with the endogenous defense mechanisms that fight ROS, Special em phasis is placed on LMW A such as ascorbate, urate, tocopher ol, lipoic acid, and histidine-related compounds, A novel elec trochemical method, using cyclic voltammetry for the determi nation of total tissue LMW A, is described, The temporal changes in brain LMWA after CHI, as part of the response of the tissue to high ROS levels, and the correlation between the The physiological response to brain injury is ex tremely complex and involves the activation of an over lapping network of humoral, tissue, and cellular path ways, The initiating event (whether ischemia, mechani cal trauma, or infection) triggers the release of endogenous mediators, These, in turn, via successive am plification steps, initiate a cascade of molecular, cellular, and tissue responses resulting in delayed tissue edema, necrosis, and impaired function (Abbreviations used: apoE, apolipoprotein E; BBB, blood-brain bar rier; CHI, closed-head injury; LMW A, low-molecular weight antioxi dants; ROS, reactive oxygen species; SOD, superoxide dismutase.
Bioenergetic Analysis of Oxidative Metabolism Following Traumatic Brain Injury in Rats
Journal of Neurotrauma, 1994
Studies of fluid percussion-induced traumatic brain injury have shown that moderate trauma results in ionic imbalances, with resultant increases in energy demand to restore these ion gradients. Because there are also increased rates of glucose metabolism during periods of focal decline in blood flow, it has been suggested that the mitochondria may be incapable of sufficient oxidative metabolism to cope with this increased energy demand after injury and that ATP derived from substrate level phosphorylation must meet this demand. In the present study, we used phosphorus magnetic resonance spectroscopy to determine the mitochondria! capacity for oxidative phosphorylation after moderate brain trauma. Before injury, mean oxidative capacity was 54% ± 1%. After injury, mean capacity increased significantly (p < 0.001) to a maximum of 61% ± 1%, indicating that mitochondrial oxidative metabolism was enhanced after trauma. Increased oxidative capacity was accompanied by increases in ADP, AMP, and inorganic phosphate concentrations and was correlated to decreases in cytosolic phosphorylation ratio. We conclude that moderate brain trauma increases mitochondrial rate of ATP synthesis over the first 4 h posttrauma, and that during this time of increased ATP turnover, positive feedback regulation of glycolysis by increased concentrations of ADP, AMP, and inorganic phosphate contributes to maintenance of metabolic steady state.