Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Üçal, M; Kraitsy, K; Weidinger, A; Paier-Pourani, J; Patz, S; Fink, B; Molcanyi, M; Schäfer, U.
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. 2017; 34(2):475-486
Doi: 10.1089/neu.2016.4411
Web of Science
PubMed
FullText
FullText_MUG
- Leading authors Med Uni Graz
- Kraitsy Klaus
- Schäfer Ute
- Ücal Muammer
- Co-authors Med Uni Graz
- Molcanyi Marek
- Patz Silke
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- 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 μM), hippocampus (0.26 ± 0.03 μM), and cerebellum (1.24 ± 0.08 μM). 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Brain Injuries - genetics
- Brain Injuries - metabolism
- Brain Injuries - pathology
- Cerebral Cortex - injuries
- Cerebral Cortex - metabolism
- Cerebral Cortex - pathology
- Disease Models, Animal -
- Gene Expression Profiling - methods
- Glutamic Acid - genetics
- Glutamic Acid - metabolism
- Male -
- Mitochondria - genetics
- Mitochondria - metabolism
- Mitochondria - pathology
- Nitric Oxide - metabolism
- Percussion - methods
- Random Allocation -
- Rats -
- Rats, Sprague-Dawley -
- Find related publications in this database (Keywords)
- brain injury
- fluid percussion
- glutamate
- mitochondria
- NO