Free Radicals and Acute Brain Injury: Mechanisms of Oxidative Stress and Therapeutic Potentials

Bayır, Hülya; Kagan, Valerian E.

doi:10.1007/978-1-4615-1721-4_6

Cited by 1 publication

(3 citation statements)

References 148 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accordingly, oxidative stress has been associated with apoptosis, achieved via a number of pathways, including the activation of nuclear factor-kB (Martindale and Holbrook, 2002), as well as the mitochondrial release of cytochrome c and apoptosis-inducing factor (Chan, 2001). Apart from lipid peroxidation, oxidation of cellular proteins and nucleic acids also occurs (Bayir and Kagan, 2001;Chan, 2001). Previous research indicates that free radicals have been implicated directly in a number of pathologic events of the central nervous system, including increased blood-brain barrier permeability (Easton and Fraser, 1998), vasogenic oedema (Hall et al, 1992), posttraumatic microvascular damage (Kontos and Hess, 1983), and subarachnoid haemorrhage-induced vasospasm (Sano et al, 1980).…”

Section: Antioxidant Properties Of Melatoninmentioning

confidence: 99%

“…Research has identified, among the sequelae of TBI, the increased production of free radicals via a number of pathologic cascades. After TBI, there is a net increase in excitotoxicity mediated by excitatory amino acids such as glutamate and N-methyl D-aspartate, leading to an increase in intracellular calcium (Bayir and Kagan, 2001). Furthermore, the release of inflammatory cytokines and intracellular calcium induces activation of enzymes including phospholipase A 2 and cyclooxygenase 2, which stimulates the eicosanoid cascade.…”

Section: Introductionmentioning

confidence: 99%

“…The calcium influx alters mitochondrial membranes, thereby disrupting the electron transport chain, leading to the accumulation of electron-reduced oxygen intermediates. Production of free radicals, resulting from these complex interactions, generates a state of oxidative stress (Bayir and Kagan, 2001). It appears that this state plays a significant role in TBI, underscoring the potential for antioxidant therapy as neuroprotection in the clinical setting.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Endogenous Melatonin Increases in Cerebrospinal Fluid of Patients after Severe Traumatic Brain Injury and Correlates with Oxidative Stress and Metabolic Disarray

Seifman

Adamides

Nguyen

et al. 2008

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Oxidative stress plays a significant role in secondary damage after severe traumatic brain injury (TBI); and melatonin exhibits both direct and indirect antioxidant effects. Melatonin deficiency is deleterious in TBI animal models, and its administration confers neuroprotection, reducing cerebral oedema, and improving neurobehavioural outcome. This study aimed to measure the endogenous cerebrospinal fluid (CSF) and serum melatonin levels post-TBI in humans and to identify relationships with markers of oxidative stress via 8-isoprostaglandin-F 2a (isoprostane), brain metabolism and neurologic outcome. Cerebrospinal fluid and serum samples of 39 TBI patients were assessed for melatonin, isoprostane, and various metabolites. Cerebrospinal fluid but not serum melatonin levels were markedly elevated (7.28±0.92 versus 1.47±0.35 pg/mL, P < 0.0005). Isoprostane levels also increased in both CSF (127.62 ± 16.85 versus 18.28 ± 4.88 pg/mL, P < 0.0005) and serum (562.46±50.78 versus 126.15±40.08 pg/mL (P < 0.0005). A strong correlation between CSF melatonin and CSF isoprostane on day 1 after injury (r = 0.563, P = 0.002) suggests that melatonin production increases in conjunction with lipid peroxidation in TBI. Relationships between CSF melatonin and pyruvate (r = 0.369, P = 0.049) and glutamate (r = 0.373, P = 0.046) indicate that melatonin production increases with metabolic disarray. In conclusion, endogenous CSF melatonin levels increase after TBI, whereas serum levels do not. This elevation is likely to represent a response to oxidative stress and metabolic disarray, although further studies are required to elucidate these relationships.

show abstract