Underlying mechanism of subcortical brain protection during hypoxia and reoxygenation in a sheep model - Influence of α1-adrenergic signalling.

While the cerebral autoregulation sufficiently protects subcortical brain regions during hypoxia or asphyxia, the cerebral cortex is not as adequately protected, which suggests that regulation of the cerebral blood flow (CBF) is area-specific. Hypoxia was induced by inhalation of 5% oxygen, for reox...

Full description

Bibliographic Details
Main Authors: René Schiffner, Sabine Juliane Bischoff, Thomas Lehmann, Florian Rakers, Sven Rupprecht, Georg Matziolis, Harald Schubert, Matthias Schwab, Otmar Huber, Cornelius Lemke, Martin Schmidt
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5973577?pdf=render
id doaj-c67c69656b654a8fb78dc2e22fe7e69d
record_format Article
spelling doaj-c67c69656b654a8fb78dc2e22fe7e69d2020-11-25T00:40:18ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01135e019636310.1371/journal.pone.0196363Underlying mechanism of subcortical brain protection during hypoxia and reoxygenation in a sheep model - Influence of α1-adrenergic signalling.René SchiffnerSabine Juliane BischoffThomas LehmannFlorian RakersSven RupprechtGeorg MatziolisHarald SchubertMatthias SchwabOtmar HuberCornelius LemkeMartin SchmidtWhile the cerebral autoregulation sufficiently protects subcortical brain regions during hypoxia or asphyxia, the cerebral cortex is not as adequately protected, which suggests that regulation of the cerebral blood flow (CBF) is area-specific. Hypoxia was induced by inhalation of 5% oxygen, for reoxygenation 100% oxygen was used. Cortical and subcortical CBF (by laser Doppler flowmetry), blood gases, mean arterial blood pressure (MABP), heart rate and renal blood flow were constantly monitored. Low dosed urapidil was used for α1A-adrenergic receptor blockade. Western blotting was used to determine adrenergic receptor signalling mediators in brain arterioles. During hypoxia cortical CBF decreased to 72 ± 11% (mean reduction 11 ± 3%, p < 0.001) of baseline, whereas subcortical CBF increased to 168±18% (mean increase 43 ± 5%, p < 0.001). Reoxygenation led to peak CBF of 194 ± 27% in the subcortex, and restored cortical CBF. α1A-Adrenergic blockade led to minor changes in cortical CBF, but massively reduced subcortical CBF during hypoxia and reoxygenation-almost aligning CBF in both brain regions. Correlation analyses revealed that α1A-adrenergic blockade renders all CBF-responses pressure-passive during hypoxia and reoxygenation, and confirmed the necessity of α1A-adrenergic signalling for coupling of CBF-responses to oxygen saturation. Expression levels and activation state of key signalling-mediators of α1-receptors (NOSs, CREB, ERK1/2) did not differ between cortex and subcortex. The dichotomy between subcortical and cortical CBF during hypoxia and reoxygenation critically depends on α1A-adrenergic receptors, but not on differential expression of signalling-mediators: signalling through the α1A-subtype is a prerequisite for cortical/subcortical redistribution of CBF.http://europepmc.org/articles/PMC5973577?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author René Schiffner
Sabine Juliane Bischoff
Thomas Lehmann
Florian Rakers
Sven Rupprecht
Georg Matziolis
Harald Schubert
Matthias Schwab
Otmar Huber
Cornelius Lemke
Martin Schmidt
spellingShingle René Schiffner
Sabine Juliane Bischoff
Thomas Lehmann
Florian Rakers
Sven Rupprecht
Georg Matziolis
Harald Schubert
Matthias Schwab
Otmar Huber
Cornelius Lemke
Martin Schmidt
Underlying mechanism of subcortical brain protection during hypoxia and reoxygenation in a sheep model - Influence of α1-adrenergic signalling.
PLoS ONE
author_facet René Schiffner
Sabine Juliane Bischoff
Thomas Lehmann
Florian Rakers
Sven Rupprecht
Georg Matziolis
Harald Schubert
Matthias Schwab
Otmar Huber
Cornelius Lemke
Martin Schmidt
author_sort René Schiffner
title Underlying mechanism of subcortical brain protection during hypoxia and reoxygenation in a sheep model - Influence of α1-adrenergic signalling.
title_short Underlying mechanism of subcortical brain protection during hypoxia and reoxygenation in a sheep model - Influence of α1-adrenergic signalling.
title_full Underlying mechanism of subcortical brain protection during hypoxia and reoxygenation in a sheep model - Influence of α1-adrenergic signalling.
title_fullStr Underlying mechanism of subcortical brain protection during hypoxia and reoxygenation in a sheep model - Influence of α1-adrenergic signalling.
title_full_unstemmed Underlying mechanism of subcortical brain protection during hypoxia and reoxygenation in a sheep model - Influence of α1-adrenergic signalling.
title_sort underlying mechanism of subcortical brain protection during hypoxia and reoxygenation in a sheep model - influence of α1-adrenergic signalling.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2018-01-01
description While the cerebral autoregulation sufficiently protects subcortical brain regions during hypoxia or asphyxia, the cerebral cortex is not as adequately protected, which suggests that regulation of the cerebral blood flow (CBF) is area-specific. Hypoxia was induced by inhalation of 5% oxygen, for reoxygenation 100% oxygen was used. Cortical and subcortical CBF (by laser Doppler flowmetry), blood gases, mean arterial blood pressure (MABP), heart rate and renal blood flow were constantly monitored. Low dosed urapidil was used for α1A-adrenergic receptor blockade. Western blotting was used to determine adrenergic receptor signalling mediators in brain arterioles. During hypoxia cortical CBF decreased to 72 ± 11% (mean reduction 11 ± 3%, p < 0.001) of baseline, whereas subcortical CBF increased to 168±18% (mean increase 43 ± 5%, p < 0.001). Reoxygenation led to peak CBF of 194 ± 27% in the subcortex, and restored cortical CBF. α1A-Adrenergic blockade led to minor changes in cortical CBF, but massively reduced subcortical CBF during hypoxia and reoxygenation-almost aligning CBF in both brain regions. Correlation analyses revealed that α1A-adrenergic blockade renders all CBF-responses pressure-passive during hypoxia and reoxygenation, and confirmed the necessity of α1A-adrenergic signalling for coupling of CBF-responses to oxygen saturation. Expression levels and activation state of key signalling-mediators of α1-receptors (NOSs, CREB, ERK1/2) did not differ between cortex and subcortex. The dichotomy between subcortical and cortical CBF during hypoxia and reoxygenation critically depends on α1A-adrenergic receptors, but not on differential expression of signalling-mediators: signalling through the α1A-subtype is a prerequisite for cortical/subcortical redistribution of CBF.
url http://europepmc.org/articles/PMC5973577?pdf=render
work_keys_str_mv AT reneschiffner underlyingmechanismofsubcorticalbrainprotectionduringhypoxiaandreoxygenationinasheepmodelinfluenceofa1adrenergicsignalling
AT sabinejulianebischoff underlyingmechanismofsubcorticalbrainprotectionduringhypoxiaandreoxygenationinasheepmodelinfluenceofa1adrenergicsignalling
AT thomaslehmann underlyingmechanismofsubcorticalbrainprotectionduringhypoxiaandreoxygenationinasheepmodelinfluenceofa1adrenergicsignalling
AT florianrakers underlyingmechanismofsubcorticalbrainprotectionduringhypoxiaandreoxygenationinasheepmodelinfluenceofa1adrenergicsignalling
AT svenrupprecht underlyingmechanismofsubcorticalbrainprotectionduringhypoxiaandreoxygenationinasheepmodelinfluenceofa1adrenergicsignalling
AT georgmatziolis underlyingmechanismofsubcorticalbrainprotectionduringhypoxiaandreoxygenationinasheepmodelinfluenceofa1adrenergicsignalling
AT haraldschubert underlyingmechanismofsubcorticalbrainprotectionduringhypoxiaandreoxygenationinasheepmodelinfluenceofa1adrenergicsignalling
AT matthiasschwab underlyingmechanismofsubcorticalbrainprotectionduringhypoxiaandreoxygenationinasheepmodelinfluenceofa1adrenergicsignalling
AT otmarhuber underlyingmechanismofsubcorticalbrainprotectionduringhypoxiaandreoxygenationinasheepmodelinfluenceofa1adrenergicsignalling
AT corneliuslemke underlyingmechanismofsubcorticalbrainprotectionduringhypoxiaandreoxygenationinasheepmodelinfluenceofa1adrenergicsignalling
AT martinschmidt underlyingmechanismofsubcorticalbrainprotectionduringhypoxiaandreoxygenationinasheepmodelinfluenceofa1adrenergicsignalling
_version_ 1725291065722798080