Cerebral vasculature is the major target of oxidative protein alterations in bacterial meningitis

Schaper, Manuela; Gergely, Suzanne; Lykkesfeldt, Jens; Zbären, Jakob; Leib, Stephen L.; Täuber, Martin G.; Christen, Stephan (2002). Cerebral vasculature is the major target of oxidative protein alterations in bacterial meningitis. Journal of neuropathology and experimental neurology, 61(7), pp. 605-13. Hagerstown, Md.: Lippincott Williams & Wilkins

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We have previously shown that antioxidants such as a-phenyl-tert-butyl nitrone or N-acetylcysteine attenuate cortical neuronal injury in infant rats with bacterial meningitis, suggesting that oxidative alterations play an important role in this disease. However, the precise mechanism(s) by which antioxidants inhibit this injury remain(s) unclear. We therefore studied the extent and location of protein oxidation in the brain using various biochemical and immunochemical methods. In cortical parenchyma, a trend for increased protein carbonyls was not evident until 21 hours after infection and the activity of glutamine synthetase (another index of protein oxidation) remained unchanged. Consistent with these results, there was no evidence for oxidative alterations in the cortex by various immunohistochemical methods even in cortical lesions. In contrast, there was a marked increase in carbonyls, 4-hydroxynonenal protein adducts and manganese superoxide dismutase in the cerebral vasculature. Elevated lipid peroxidation was also observed in cerebrospinal fluid and occasionally in the hippocampus. All of these oxidative alterations were inhibited by treatment of infected animals with N-acetylcysteine or alpha-phenyl-tert-butyl nitrone. Because N-acetylcysteine does not readily cross the blood-brain barrier and has no effect on the loss of endogenous brain antioxidants, its neuroprotective effect is likely based on extraparenchymal action such as inhibition of vascular oxidative alterations.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
UniBE Contributor:	Zbären, Jakob, Leib, Stephen, Täuber, Martin G., Christen, Stephan
Subjects:	500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health
ISSN:	0022-3069
ISBN:	12125739
Publisher:	Lippincott Williams & Wilkins
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:56
Last Modified:	05 Dec 2022 14:17
PubMed ID:	12125739
Web of Science ID:	000176604600004
URI:	https://boris.unibe.ch/id/eprint/23689 (FactScience: 43482)