Universität zu Köln

Uecal, Muammer, Kraitsy, Klaus, Weidinger, Adelheid, Paier-Pourani, Jamile, Patz, Silke, Fink, Bruno, Molcanyi, Marek and Schaefer, Ute (2017). Comprehensive Profiling of Modulation of Nitric Oxide Levels and Mitochondrial Activity in the Injured Brain: An Experimental Study Based on the Fluid Percussion Injury Model in Rats. J. Neurotrauma, 34 (2). S. 475 - 487. NEW ROCHELLE: MARY ANN LIEBERT, INC. ISSN 1557-9042

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Abstract

Nitric oxide (NO) has frequently been associated with secondary damage after brain injury. However, average NO levels in different brain regions before and after traumatic brain injury (TBI) and its role in post-TBI mitochondrial dysfunction remain unclear. In this comprehensive profiling study, we demonstrate for the first time that basal NO levels vary significantly in the healthy cortex (0.44 +/- 0.04 mu M), hippocampus (0.26 +/- 0.03 mu M), and cerebellum (1.24 +/- 0.08 mu M). Within 4 h of severe lateral fluid percussion injury, NO levels almost doubled in these regions, thereby preserving regional differences in NO levels. TBI-induced NO generation was associated with inducible NO synthase (iNOS) increase in ipsilateral but not in contralateral regions. The transient NO increase resulted in a persistent tyrosine nitration adjacent to the injury site. Nitrosative stress-associated cell loss via apoptosis and receptor-interacting serine/threonine-protein kinase 3 (RIPK3)-mediated necrosis were also observed in the ipsilateral cortex, despite high levels of NO in the contralateral cortex. NO-mediated impairment of mitochondrial state 3 respiration dependent on complex I substrates was transient and confined to the ipsilateral cortex. Our results demonstrate that NO dynamics and associated effects differ in various regions of the injured brain. A potential association between the observed mitochondrial electron flow through complex I, but not complex II, and the modulation of TBI induced NO levels in different brain regions has to be prospectively analyzed in more detail.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Uecal, Muammer UNSPECIFIED UNSPECIFIED UNSPECIFIED Kraitsy, Klaus UNSPECIFIED UNSPECIFIED UNSPECIFIED Weidinger, Adelheid UNSPECIFIED UNSPECIFIED UNSPECIFIED Paier-Pourani, Jamile UNSPECIFIED UNSPECIFIED UNSPECIFIED Patz, Silke UNSPECIFIED UNSPECIFIED UNSPECIFIED Fink, Bruno UNSPECIFIED UNSPECIFIED UNSPECIFIED Molcanyi, Marek UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaefer, Ute UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-242473
DOI:	10.1089/neu.2016.4411
Journal or Publication Title:	J. Neurotrauma
Volume:	34
Number:	2
Page Range:	S. 475 - 487
Date:	2017
Publisher:	MARY ANN LIEBERT, INC
Place of Publication:	NEW ROCHELLE
ISSN:	1557-9042
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CEREBRAL-BLOOD-FLOW; CONTROLLED CORTICAL IMPACT; APOPTOTIC CELL-DEATH; OXIDATIVE DAMAGE; PROGRAMMED NECROSIS; SYNTHASE ACTIVATION; NADPH-OXIDASE; TIME-COURSE; L-ARGININE; COMPLEX-I Multiple languages Critical Care Medicine; Clinical Neurology; Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/24247