Oxidative Stress in Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) is a major healthcare concern, constituting a major cause of death and disability throughout the world. Among the factors leading to TBI outcome are biochemical cascades which occur in response to primary and secondary injury. These mechanisms generate oxidative stress, an imbalance between oxidant and antioxidant agents that can result in neural dysfunction and death. After TBI, an assembly of oxidative stress markers (carbonylated proteins, lipid peroxides, reactive oxygen and reactive nitrogen species) are produced in the brain, while antioxidant defense enzymes decrease (GSH, ratio GSH/GSSG, GPx, GR, GST, G-6PD, SOD, CAT). This imbalance is directly related to the pathogenesis of TBI. Therefore, the development of antioxidant strategies is of primary interest in ongoing efforts to optimize brain injury treatment. The success of any drug intervention strategy relies, in part, on knowledge of the optimal dosage and therapeutic window for its administration. But while the enzymes involved in oxidative stress have been identified, the temporal course of this imbalance following TBI has yet to be determined. This would explain why most antioxidant strategies developed to treat patients with TBI have failed.

Lactate Storm Marks Cerebral Metabolism following Brain Trauma

“…Significant activation of astrocytes (glial fibrillary acidic protein), neuronal injury/inflammation with the presence of dark neurons (H&E), and tauopathy (Tau immunohistology) support the observation of neuronal and glial pathology, which in turn would explain perturbed metabolism of the cell population as shown by the MR spectroscopy data. Severe head trauma results in oxidative stress reflected by the rapid accumulation of oxidative stress markers with a decrease in antioxidant defense enzymes (52)(53)(54). Oxidative stress is known to induce the formation of hyperphosphorylated Tau, consistent with the results reported here (55,56).…”

Cerium Oxide Nanoparticles Improve Outcome afterIn VitroandIn VivoMild Traumatic Brain Injury

“…To further determine the efficacy of CeONPs in mTBI, we investigated their ability to mitigate the pathological depletion of endogenous antioxidant systems 7,8,11 using an in vivo model. Both injection paradigms utilized showed significant improvement of catalase, SOD, and GSH/GSSG ratios compared with the injury-only group (Fig.…”

“…[2][3][4][5][6] Despite endogenous brain antioxidants such as superoxide dismutase (SOD), catalase, and glutathione (GSH); excessive free radical production after TBI overwhelms endogenous defenses, leaving the brain in an abnormal state of high oxidative stress, persisting into the chronic phase after injury. 7,8 This increase in oxidative stress has been coupled to alterations in cognitive performance. [9][10][11] Traditional antioxidants have been utilized in attempts to mitigate the pathological effects of TBI, [12][13][14] but have met with limited success in clinical trials.…”

APOE4, oxidative stress and decreased repair capacity - a no-brainer. Faulty lipid metabolism and increased levels of oxidative damage may be risk factors in the pathogenesis of late-onset dementia

“…Recently, a theory that late-onset neurodegenerative diseases had a common pathogenetic mechanism based largely on premature neuronal death triggered and promoted by unrepaired oxidative damage has been developed [27]. Oxidative stress has been strongly suspected as the main culprit for neuronal loss in ischemic strokes, brain microhaemorrhages and head trauma [28][29][30]. Oxidative phosphorylation is the main source of oxidative stress in living cells.…”