title: Increased S-nitrosothiols and S-nitrosoalbumin in cerebrospinal fluid after severe traumatic brain injury in infants and children: indirect association with intracranial pressure.
abstract: Nitric oxide (NO) is implicated in both secondary damage and recovery after traumatic brain injury (TBI). Transfer of NO groups to cysteine sulfhydryls on proteins produces S-nitrosothiols (RSNO). S-nitrosothiols may be neuroprotective after TBI by nitrosylation of N-methyl-D-aspartate receptor and caspases. S-nitrosothiols release NO on decomposition for which endogenous reductants (i.e., ascorbate) are essential, and ascorbate is depleted in cerebrospinal fluid (CSF) after pediatric TBI. This study examined the presence and decomposition of RSNO in CSF and the association between CSF RSNO level and physiologic parameters after severe TBI. Cerebrospinal fluid samples (n = 72) were obtained from 18 infants and children on days 1 to 3 after severe TBI (Glasgow Coma Scale score < 8) and 18 controls. Cerebrospinal fluid RSNO levels assessed by fluorometric assay peaked on day 3 versus control (1.42 +/- 0.11 micromol/L vs. 0.86 +/- 0.04, P< 0.05). S-nitrosoalbumin levels were also higher after TBI (n = 8, 0.99 +/- 0.09 micromol/L on day 3 vs. n = 6, 0.42 +/- 0.02 in controls, P< 0.05). S-nitrosoalbumin decomposition was decreased after TBI. Multivariate analysis showed an inverse relation between CSF RSNO and intracranial pressure and a direct relation with barbiturate treatment. Using a novel assay, the presence of RSNO and S-nitrosoalbumin in human CSF, an approximately 1.7-fold increase after TBI, and an association with low intracranial pressure are reported, supporting a possible neuroprotective role for RSNO. The increase in RSNO may result from increased NO production and/or decreased RSNO decomposition.
authors.affiliation: Safar Center for Resuscitation Research, University of Pittsburgh Medical Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pennsylvania 15213, USA.
authors.forename: Hülya
authors.initials: H
authors.lastname: Bayir
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Kochanek
authors.forename: Shang-Xi
authors.initials: SX
authors.lastname: Liu
authors.forename: Antonio
authors.initials: A
authors.lastname: Arroyo
authors.forename: Anatoly
authors.initials: A
authors.lastname: Osipov
authors.forename: Jianfei
authors.initials: J
authors.lastname: Jiang
authors.forename: Stephan
authors.initials: S
authors.lastname: Wisniewski
authors.forename: P David
authors.initials: PD
authors.lastname: Adelson
authors.forename: Steven H
authors.initials: SH
authors.lastname: Graham
authors.forename: Valerian E
authors.initials: VE
authors.lastname: Kagan
mesh_terms: D000293:Adolescent; D000418:Albumins / Q000134:cerebrospinal fluid*; D001930:Brain Injuries / Q000134:cerebrospinal fluid* / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007427:Intracranial Pressure; D009603:Nitroso Compounds / Q000134:cerebrospinal fluid*; D013438:Sulfhydryl Compounds / Q000134:cerebrospinal fluid*; D015599:Trauma Severity Indices
chemical_list: D000418:Albumins; D009603:Nitroso Compounds; D013438:Sulfhydryl Compounds