Hosmann 2020 Acta Neurochir (Wien): Difference between revisions
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{{Publication | {{Publication | ||
|title=Hosmann A, Milivojev N, Dumitrescu S, Reinprecht A, Weidinger A, Kozlov AV (2020) Cerebral nitric oxide and mitochondrial function in patients suffering aneurysmal subarachnoid hemorrhage-a translational approach. Acta Neurochir (Wien) | |title=Hosmann A, Milivojev N, Dumitrescu S, Reinprecht A, Weidinger A, Kozlov AV (2020) Cerebral nitric oxide and mitochondrial function in patients suffering aneurysmal subarachnoid hemorrhage-a translational approach. Acta Neurochir (Wien) 163:139-49. | ||
|info=[https://pubmed.ncbi.nlm.nih.gov/32839865 PMID: 32839865 Open Access] | |info=[https://pubmed.ncbi.nlm.nih.gov/32839865 PMID: 32839865 Open Access] | ||
|authors=Hosmann Arthur, Milivojev Nadja, Dumitrescu Sergiu, Reinprecht Andrea, Weidinger Adelheid, Kozlov Andrey V | |authors=Hosmann Arthur, Milivojev Nadja, Dumitrescu Sergiu, Reinprecht Andrea, Weidinger Adelheid, Kozlov Andrey V | ||
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|keywords=Microdialysis, Mitochondrial function, Nitric oxide, Subarachnoid hemorrhage | |keywords=Microdialysis, Mitochondrial function, Nitric oxide, Subarachnoid hemorrhage | ||
|editor=[[Plangger M]] | |editor=[[Plangger M]] | ||
|mipnetlab=AT Vienna Kozlov AV | |||
}} | }} | ||
{{Labeling | {{Labeling |
Latest revision as of 18:14, 20 October 2021
Hosmann A, Milivojev N, Dumitrescu S, Reinprecht A, Weidinger A, Kozlov AV (2020) Cerebral nitric oxide and mitochondrial function in patients suffering aneurysmal subarachnoid hemorrhage-a translational approach. Acta Neurochir (Wien) 163:139-49. |
Hosmann Arthur, Milivojev Nadja, Dumitrescu Sergiu, Reinprecht Andrea, Weidinger Adelheid, Kozlov Andrey V (2020) Acta Neurochir (Wien)
Abstract: Cerebral ischemia and neuroinflammation following aneurysmal subarachnoid hemorrhage (SAH) are major contributors to poor neurological outcome. Our study set out to investigate in an exploratory approach the interaction between NO and energy metabolism following SAH as both hypoxia and inflammation are known to affect nitric oxide (NO) metabolism and NO in turn affects mitochondria.
In seven patients under continuous multimodality neuromonitoring suffering poor-grade aneurysmal SAH, cerebral metabolism and NO levels (determined as a sum of nitrite plus nitrate) were determined in cerebral microdialysate for 14 days following SAH. In additional ex vivo experiments, rat cortex homogenate was subjected to the NO concentrations determined in SAH patients to test whether these NO concentrations impair mitochondrial function (determined by means of high-resolution respirometry).
NO levels showed biphasic kinetics with drastically increased levels during the first 7 days (74.5 ยฑ 29.9 ฮผM) and significantly lower levels thereafter (47.5 ยฑ 18.7 ฮผM; p = 0.02). Only during the first 7 days, NO levels showed a strong negative correlation with brain tissue oxygen tension (r = - 0.78; p < 0.001) and a positive correlation with cerebral lactate (r = 0.79; p < 0.001), pyruvate (r = 0.68; p < 0.001), glutamate (r = 0.65; p < 0.001), as well as the lactate-pyruvate ratio (r = 0.48; p = 0.01), suggesting mitochondrial dysfunction. Ex vivo experiments confirmed that the increase in NO levels determined in patients during the acute phase is sufficient to impair mitochondrial function (p < 0.001). Mitochondrial respiration was inhibited irrespectively of whether glutamate (substrate of complex I) or succinate (substrate of complex II) was used as mitochondrial substrate suggesting the inhibition of mitochondrial complex IV. The latter was confirmed by direct determination of complex IV activity.
Exploratory analysis of our data suggests that during the acute phase of SAH, NO plays a key role in the neuronal damage impairing mitochondrial function and facilitating accumulation of mitochondrial substrate; further studies are required to understand mechanisms underlying this observation. โข Keywords: Microdialysis, Mitochondrial function, Nitric oxide, Subarachnoid hemorrhage โข Bioblast editor: Plangger M โข O2k-Network Lab: AT Vienna Kozlov AV
Labels: MiParea: Respiration, Pharmacology;toxicology
Organism: Rat
Tissue;cell: Nervous system
Preparation: Homogenate
Coupling state: OXPHOS
Pathway: N, S, CIV, ROX
HRR: Oxygraph-2k
2020-09