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.
Highlights
Regulation of cerebral blood flow (CBF) is accomplished by several mechanisms acting on multiple levels
The novel findings of the present study are that traumatic brain injury (1) significantly reduces flow-induced constriction of middle cerebral arteries, (2) which corresponds to the reduction of arachidonic acid- 20-hydroxyeicosatetraenoic acid (20-HETE)- and thromboxane receptor agonist-induced constrictions
We propose that traumatic brain injury (TBI) interferes with the function of CYP450 4A, thereby with the production of constrictor prostaglandins and with the sensitivity of TP receptors to these prostaglandins, resulting in a substantially reduced flow-induced constrictor response
Summary
Regulation of cerebral blood flow (CBF) is accomplished by several mechanisms acting on multiple levels. Some of them are serving local needs [1,2,3,4,5], whereas others ensure that an appropriate volume of the blood is flowing into the brain seated in the rigid cranium. These later ones are important because they can prevent increases intracranial pressure by preventing large amount of blood volume entering the brain [4]. It seems that both mechanisms are necessary to elicit autoregulation by providing together frank constrictions of cerebral arteries that sufficiently increase vascular resistance to prevent increases in blood flow when perfusion pressure increases [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
