title: Endogenous melatonin increases in cerebrospinal fluid of patients after severe traumatic brain injury and correlates with oxidative stress and metabolic disarray.
abstract: 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-F2alpha (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.
authors.affiliation: National Trauma Research Institute, The Alfred, Melbourne, Victoria, Australia.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Seifman
authors.forename: Alexios A
authors.initials: AA
authors.lastname: Adamides
authors.forename: Phuong N
authors.initials: PN
authors.lastname: Nguyen
authors.forename: Shirley A
authors.initials: SA
authors.lastname: Vallance
authors.forename: David James
authors.initials: DJ
authors.lastname: Cooper
authors.forename: Thomas
authors.initials: T
authors.lastname: Kossmann
authors.forename: Jeffrey V
authors.initials: JV
authors.lastname: Rosenfeld
authors.forename: M Cristina
authors.initials: MC
authors.lastname: Morganti-Kossmann
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000378:metabolism*; D001930:Brain Injuries / Q000097:blood / Q000134:cerebrospinal fluid*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D028421:Isoprostanes / Q000134:cerebrospinal fluid; D008297:Male; D008550:Melatonin / Q000097:blood / Q000134:cerebrospinal fluid*; D017551:Microdialysis; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*
chemical_list: D028421:Isoprostanes; D008550:Melatonin