Oxidative stress following traumatic brain injury in rats

Awasthi, Deepak; Church, Daniel F.; Torbati, Dan; Carey, Michael E.; Pryor, William A.

doi:10.1016/s0090-3019(96)00461-2

Cited by 95 publications

(63 citation statements)

References 46 publications

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“…Enhanced oxidative stress associated with increased production of free radicals has been implicated in experimental TBI-induced disruption of neuronal homeostasis (7,9,10,39). Detailed quantitative assessments of biomarkers of oxidative stress as well as depletion of antioxidant reserves after TBI in humans, however, have not been conducted.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Antioxidant Reserves and Oxidative Stress in Cerebrospinal Fluid after Severe Traumatic Brain Injury in Infants and Children

et al. 2002

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Studies in experimental traumatic brain injury (TBI) support a key role for oxidative stress. The degree of oxidative injury in clinical TBI, however, remains to be defined. We assessed antioxidant defenses and oxidative stress in pediatric TBI by applying a comprehensive battery of assays to cerebrospinal fluid samples. Using a protocol approved by our institutional review board, 87 cerebrospinal fluid samples from 11 infants and children with severe TBI (Glasgow Coma Scale score Յ8) and 8 controls were studied. Cerebrospinal fluid was drained as standard care after TBI. CSF was assessed on d 1, 2, and 5-7 after ventricular drain placement. Biochemical markers of oxidative stress included F 2 -isoprostane and protein sulfhydryl (detected by ELISA and fluorescence assay, respectively). Antioxidant defenses were measured by determination of total antioxidant reserve (via chemiluminescence assay), and ascorbate (via HPLC) and glutathione (via fluorescence assay) concentrations. Free radical production (ascorbate radical) was assessed by electron paramagnetic resonance spectroscopy. F 2 -isoprostane was markedly increased versus control, maximal on d 1 (93.8 Ϯ 30.8 pg/mL versus 7.6 Ϯ 5.1 pg/mL, p Ͻ 0.05). Total antioxidant reserve was reduced versus control. Reduction was maximal on Abbreviations TBI, traumatic brain injury CSF, cerebrospinal fluid EPR, electron paramagnetic resonance spectroscopy LMWA, low-molecular-weight antioxidants SOD, superoxide dismutase GSH, glutathione GCS, Glasgow Coma Scale AAPH, 2,2'-azobis(2-amidinopropane)dihydrochloride Trauma is the leading cause of death in children. Severe TBI is an important contributor to this mortality and to associated morbidity. TBI triggers a pathway of neuronal death involving loss of cellular calcium homeostasis, tissue acidosis, and oxidative stress (1). Data from experimental TBI support an important role for oxidative injury in early neuronal and vascular damage after TBI (2-5), as well as in secondary delete-

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Section: Discussionmentioning

confidence: 99%

Assessment of Antioxidant Reserves and Oxidative Stress in Cerebrospinal Fluid after Severe Traumatic Brain Injury in Infants and Children

et al. 2002

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“…2), suggesting that cerebral metabolism was still engaged mainly in restoring the altered metabolic functions indispensable for cell homeostasis and survival. The complex neurotoxic cascade, directly triggered by the traumatic insult and extending over days or weeks includes changes in ionic fluxes (40), hyperglycolysis (80), indiscriminate glutamate release (2,63), calcium overloading (24,75), mitochondrial dysfunction (27,77), and impaired oxidative metabolism (4,73). Hence, it might be reasonable to hypothesize that, in a sort of "list of biochemical priorities," these changes have intrinsic greater detrimental effects on cell survival than the NAA resynthesis, which will finally be completed only after normalization of these more important metabolic alterations (79).…”

Section: Second Impact Syndrome: a Concept To Broaden?mentioning

confidence: 99%

Temporal Window of Metabolic Brain Vulnerability to Concussion

et al. 2008

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OBJECTIVE:In the present study, the occurrence of the temporal window of brain vulnerability was evaluated in concussed athletes by measuring N-acetylaspartate (NAA) using proton magnetic resonance ( 1 H-MR) spectroscopy. METHODS: Thirteen nonprofessional athletes who had a sport-related concussive head injury were examined for NAA determination by means of 1 H-MR spectroscopy at 3, 15, and 30 days postinjury. All athletes but three suspended their physical activity. Those who continued their training had a second concussive event and underwent further examination at 45 days from the initial injury. The single case of one professional boxer, who was studied before the match and 4, 7, 15, and 30 days after a knockout, is also presented. Before each magnetic resonance examination, patients were asked for symptoms of mild traumatic brain injury, including physical, cognitive, emotional, and sleep disturbances. Data for 1 H-MR spectroscopy recorded in five normal, age-matched, control volunteers, who were previously screened to exclude previous head injuries, were used for comparison. Semiquantitative analysis of NAA relative to creatine (Cr)-and choline (Cho)-containing compounds was performed from proton spectra obtained with a 3-T magnetic resonance system. RESULTS: Regarding the values of the NAA-to-Cr ratio (2.21 Ϯ 0.11) recorded in control patients, singly concussed athletes, at 3 days after the concussion, showed a decrease of 18.5% (1.80 Ϯ 0.04; P Ͻ 0.001). Only a modest 3% recovery was observed at 15 days (1.88 Ϯ 0.1; P Ͻ 0.001); at 30 days postinjury, the NAA-to-Cr ratio was 2.15 Ϯ 0.1, revealing full metabolic recovery with values not significantly different from those of control patients. These patients declared complete resolution of symptoms at the time of the 3-day study. The three patients who had a second concussive injury before the 15-day study showed an identical decrease of the NAA-to-Cr ratio at 3 days (1.78 Ϯ 0.08); however, at 15 days after the second injury, a further diminution of the NAA-to-Cr ratio occurred (1.72 Ϯ 0.07; P Ͻ 0.05 with respect to singly concussed athletes). At 30 days, the NAAto-Cr ratio was 1.82 Ϯ 0.1, and at 45 days postinjury, the NAA-to-Cr ratio showed complete recovery (2.07 Ϯ 0.1; not significant with respect to control patients). This group of patients declared a complete resolution of symptoms at the time of the 30-day study. CONCLUSION: Results of this pilot study carried out in a cohort of singly and doubly concussed athletes, examined by 1 H-MR spectroscopy for their NAA cerebral content at different time points after concussive events, demonstrate that also in humans, concussion opens a temporal window of brain metabolic imbalance, the closure of which does not coincide with resolution of clinical symptoms. The recovery of brain metabolism is not linearly related to time. A second concussive event prolonged the time of NAA normalization by 15 days. Although needing confirmation in a larger group of patients, these results show that NAA measurement by 1 H-MR spe...

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“…Moreover, peroxidative reactions themselves initiate complex chain-reactions which generate even more free radicals (57). These free radicals, along with other damaging neurochemical events, have been shown to play an important role in the pathophysiology of CNS injury (58,59). Indeed, the increase in reactive oxygen species in the brain soon after CNS injury correlates with formation of cerebral oedema, secondary ischemia, and impairment of microvascular regulation (56,(60)(61)(62)(63).…”

Section: The Role Of Magnesiummentioning

confidence: 99%

Regulation of intracellular free magnesium in central nervous system injury

Vink¹

2000

Front Biosci

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Oxidative stress following traumatic brain injury in rats

Cited by 95 publications

References 46 publications

Assessment of Antioxidant Reserves and Oxidative Stress in Cerebrospinal Fluid after Severe Traumatic Brain Injury in Infants and Children

Assessment of Antioxidant Reserves and Oxidative Stress in Cerebrospinal Fluid after Severe Traumatic Brain Injury in Infants and Children

Temporal Window of Metabolic Brain Vulnerability to Concussion

Regulation of intracellular free magnesium in central nervous system injury

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