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Volume 22
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10.3390/ijms22126624
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Article

Molecular Pathomechanisms of Impaired Flow-Induced Constriction of Cerebral Arteries Following Traumatic Brain Injury: A Potential Impact on Cerebral Autoregulation

by
Annamaria Szenasi
1,2,
Krisztina Amrein
3,
Endre Czeiter
3,
Nikolett Szarka
4,
Peter Toth
3,4 and
Akos Koller
1,2,5,6,*
1
Department of Translational Medicine, Faculty of Medicine, Semmelweis University, 1085 Budapest, Hungary
2
Department of Morphology and Physiology, Faculty of Health Sciences, Semmelweis University, 1085 Budapest, Hungary
3
Department of Neurosurgery and Szentágothai Research Center, University of Pecs, Medical School, 7623 Pecs, Hungary
4
MTA-PTE Clinical Neuroscience MR Research Group, 7623 Pecs, Hungary
5
Research Center for Sports Physiology, University of Physical Education, 1123 Budapest, Hungary
6
Department of Physiology, New York Medical College, Valhalla, NY 10595, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(12), 6624; https://doi.org/10.3390/ijms22126624
Submission received: 30 April 2021 / Revised: 11 June 2021 / Accepted: 16 June 2021 / Published: 21 June 2021
(This article belongs to the Special Issue Molecular Vascular Physiology)
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Abstract

(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, p < 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, 10−7 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 (10−7 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.
Keywords: hemodynamic forces; diameter; autoregulation; arachidonic acid; CYP450 4A; TXA2 receptors hemodynamic forces; diameter; autoregulation; arachidonic acid; CYP450 4A; TXA2 receptors

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MDPI and ACS Style

Szenasi, A.; Amrein, K.; Czeiter, E.; Szarka, N.; Toth, P.; Koller, A. Molecular Pathomechanisms of Impaired Flow-Induced Constriction of Cerebral Arteries Following Traumatic Brain Injury: A Potential Impact on Cerebral Autoregulation. Int. J. Mol. Sci. 2021, 22, 6624. https://doi.org/10.3390/ijms22126624

AMA Style

Szenasi A, Amrein K, Czeiter E, Szarka N, Toth P, Koller A. 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. 2021; 22(12):6624. https://doi.org/10.3390/ijms22126624

Chicago/Turabian Style

Szenasi, Annamaria, Krisztina Amrein, Endre Czeiter, Nikolett Szarka, Peter Toth, and Akos Koller. 2021. "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 22, no. 12: 6624. https://doi.org/10.3390/ijms22126624

APA Style

Szenasi, A., Amrein, K., Czeiter, E., Szarka, N., Toth, P., & Koller, A. (2021). 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, 22(12), 6624. https://doi.org/10.3390/ijms22126624

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