Oxidative stress in bacterial meningitis in humans.
OBJECTIVE
To study reactive nitrogen species-mediated oxidative brain damage and antioxidant defenses in patients with acute bacterial meningitis.


METHODS
Nitrotyrosine (a widely used marker for the formation of reactive nitrogen species, such as peroxynitrite) and the lipid peroxidation product 4-hydroxynonenal were detected by immunohistochemistry in brain specimens obtained at autopsy. CSF concentrations of nitrotyrosine were quantified by ELISA. CSF and serum concentrations of ascorbic acid, uric acid, and its oxidation product allantoin were determined by high-pressure liquid chromatography.


RESULTS
Tyrosine nitration was strongly increased during meningitis. It was most evident in inflammatory cells and blood vessels in the subarachnoid space. The same cell types stained positive for the lipid peroxidation marker 4-hydroxynonenal, suggesting that reactive nitrogen species contribute to oxidative brain damage during meningitis. High CSF nitrotyrosine concentrations were associated with an unfavorable outcome according to the Glasgow Outcome Score. In the CSF, the increase of nitrotyrosine was accompanied by a depletion of the antioxidant ascorbic acid and an increased oxidation of the natural peroxynitrite scavenger uric acid to allantoin.


CONCLUSIONS
These findings indicate that oxidative stress due to reactive nitrogen species and altered antioxidant defenses are involved in the pathophysiology of bacterial meningitis in humans.
Kastenbauer
S
S
Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany.
Koedel
U
U
Becker
B F
BF
Pfister
H W
HW
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000447:Aldehydes / Q000378:metabolism*; D000481:Allantoin / Q000097:blood / Q000134:cerebrospinal fluid; D001205:Ascorbic Acid / Q000097:blood / Q000134:cerebrospinal fluid; D001921:Brain / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D005260:Female; D016166:Free Radical Scavengers / Q000097:blood / Q000134:cerebrospinal fluid; D023261:Glasgow Outcome Scale; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D016920:Meningitis, Bacterial / Q000378:metabolism*; D008875:Middle Aged; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018384:Oxidative Stress; D026361:Reactive Nitrogen Species / Q000378:metabolism; D013223:Statistics as Topic; D016896:Treatment Outcome; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid / Q000378:metabolism*; D014527:Uric Acid / Q000097:blood / Q000134:cerebrospinal fluid
D000447:Aldehydes; D015853:Cysteine Proteinase Inhibitors; D016166:Free Radical Scavengers; D026361:Reactive Nitrogen Species; D014527:Uric Acid; D000481:Allantoin; C002744:3-nitrotyrosine; D014443:Tyrosine; C027576:4-hydroxy-2-nonenal; D001205:Ascorbic Acid