Molecular Pathomechanisms of Impaired Flow-Induced Constriction of Cerebral Arteries Following Traumatic Brain Injury: A Potential Impact on Cerebral Autoregulation
(1) Background: Traumatic brain injury (TBI) frequently occurs worldwide, resulting in high morbidity and mortality. Here, we hypothesized that TBI impairs an autoregulatory mechanism, namely the flow-induced constriction of isolated rat middle cerebral arteries (MCAs). (2) Methods: TBI was induced...
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doaj-fc5ad220ef9c480093124cace75ce5972021-07-01T00:45:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-01226624662410.3390/ijms22126624Molecular Pathomechanisms of Impaired Flow-Induced Constriction of Cerebral Arteries Following Traumatic Brain Injury: A Potential Impact on Cerebral AutoregulationAnnamaria Szenasi0Krisztina Amrein1Endre Czeiter2Nikolett Szarka3Peter Toth4Akos Koller5Department of Translational Medicine, Faculty of Medicine, Semmelweis University, 1085 Budapest, HungaryDepartment of Neurosurgery and Szentágothai Research Center, University of Pecs, Medical School, 7623 Pecs, HungaryDepartment of Neurosurgery and Szentágothai Research Center, University of Pecs, Medical School, 7623 Pecs, HungaryMTA-PTE Clinical Neuroscience MR Research Group, 7623 Pecs, HungaryDepartment of Neurosurgery and Szentágothai Research Center, University of Pecs, Medical School, 7623 Pecs, HungaryDepartment of Translational Medicine, Faculty of Medicine, Semmelweis University, 1085 Budapest, Hungary(1) Background: Traumatic brain injury (TBI) frequently occurs worldwide, resulting in high morbidity and mortality. Here, we hypothesized that TBI impairs an autoregulatory mechanism, namely the flow-induced constriction of isolated rat middle cerebral arteries (MCAs). (2) Methods: TBI was induced in anaesthetized rats by weight drop model, and then MCAs were isolated and transferred into a pressure-flow chamber. The internal diameter was measured by a video-microscopy. (3) Results: In MCAs from intact rats, increases in flow and pressure + flow elicited constrictions (−26 ± 1.9 µm and −52 ± 2.8 µm, <i>p</i> < 0.05), which were significantly reduced after TBI or in the presence of thromboxane-prostanoid (TP receptor) antagonist SQ 29,548. Flow-induced constrictions were significantly reduced by HET0016, inhibitor of cytochrome P450 4A (CYP450 4A). Arachidonic acid, (AA, 10<sup>−7</sup> M), and CYP-450 4A metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) elicited constrictions of intact MCA (−26 ± 2.3% and −31 ± 3.6%), which were significantly reduced after TBI (to 11 ± 1.3% and −16 ±2.5%). The TP receptor agonist U46619 (10<sup>−7</sup> M) elicited substantial constrictions of MCA from intact rats (−21 ± 3.3%), which were also significantly reduced, after TBI (to −16 ± 2.4%). (4) Conclusions: Flow-induced constrictor response of MCA is impaired by traumatic brain injury, likely due to the reduced ability of cytochrome P450 4A to convert arachidonic acid to constrictor prostaglandins and the mitigated sensitivity of thromboxane-prostanoid receptors.https://www.mdpi.com/1422-0067/22/12/6624hemodynamic forcesdiameterautoregulationarachidonic acidCYP450 4ATXA<sub>2</sub> receptors |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Annamaria Szenasi Krisztina Amrein Endre Czeiter Nikolett Szarka Peter Toth Akos Koller |
spellingShingle |
Annamaria Szenasi Krisztina Amrein Endre Czeiter Nikolett Szarka Peter Toth Akos Koller Molecular Pathomechanisms of Impaired Flow-Induced Constriction of Cerebral Arteries Following Traumatic Brain Injury: A Potential Impact on Cerebral Autoregulation International Journal of Molecular Sciences hemodynamic forces diameter autoregulation arachidonic acid CYP450 4A TXA<sub>2</sub> receptors |
author_facet |
Annamaria Szenasi Krisztina Amrein Endre Czeiter Nikolett Szarka Peter Toth Akos Koller |
author_sort |
Annamaria Szenasi |
title |
Molecular Pathomechanisms of Impaired Flow-Induced Constriction of Cerebral Arteries Following Traumatic Brain Injury: A Potential Impact on Cerebral Autoregulation |
title_short |
Molecular Pathomechanisms of Impaired Flow-Induced Constriction of Cerebral Arteries Following Traumatic Brain Injury: A Potential Impact on Cerebral Autoregulation |
title_full |
Molecular Pathomechanisms of Impaired Flow-Induced Constriction of Cerebral Arteries Following Traumatic Brain Injury: A Potential Impact on Cerebral Autoregulation |
title_fullStr |
Molecular Pathomechanisms of Impaired Flow-Induced Constriction of Cerebral Arteries Following Traumatic Brain Injury: A Potential Impact on Cerebral Autoregulation |
title_full_unstemmed |
Molecular Pathomechanisms of Impaired Flow-Induced Constriction of Cerebral Arteries Following Traumatic Brain Injury: A Potential Impact on Cerebral Autoregulation |
title_sort |
molecular pathomechanisms of impaired flow-induced constriction of cerebral arteries following traumatic brain injury: a potential impact on cerebral autoregulation |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-06-01 |
description |
(1) Background: Traumatic brain injury (TBI) frequently occurs worldwide, resulting in high morbidity and mortality. Here, we hypothesized that TBI impairs an autoregulatory mechanism, namely the flow-induced constriction of isolated rat middle cerebral arteries (MCAs). (2) Methods: TBI was induced in anaesthetized rats by weight drop model, and then MCAs were isolated and transferred into a pressure-flow chamber. The internal diameter was measured by a video-microscopy. (3) Results: In MCAs from intact rats, increases in flow and pressure + flow elicited constrictions (−26 ± 1.9 µm and −52 ± 2.8 µm, <i>p</i> < 0.05), which were significantly reduced after TBI or in the presence of thromboxane-prostanoid (TP receptor) antagonist SQ 29,548. Flow-induced constrictions were significantly reduced by HET0016, inhibitor of cytochrome P450 4A (CYP450 4A). Arachidonic acid, (AA, 10<sup>−7</sup> M), and CYP-450 4A metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) elicited constrictions of intact MCA (−26 ± 2.3% and −31 ± 3.6%), which were significantly reduced after TBI (to 11 ± 1.3% and −16 ±2.5%). The TP receptor agonist U46619 (10<sup>−7</sup> M) elicited substantial constrictions of MCA from intact rats (−21 ± 3.3%), which were also significantly reduced, after TBI (to −16 ± 2.4%). (4) Conclusions: Flow-induced constrictor response of MCA is impaired by traumatic brain injury, likely due to the reduced ability of cytochrome P450 4A to convert arachidonic acid to constrictor prostaglandins and the mitigated sensitivity of thromboxane-prostanoid receptors. |
topic |
hemodynamic forces diameter autoregulation arachidonic acid CYP450 4A TXA<sub>2</sub> receptors |
url |
https://www.mdpi.com/1422-0067/22/12/6624 |
work_keys_str_mv |
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