Traumatic Brain Injury Impairs Flow‐Dependent Constrictions of Isolated Rat Middle Cerebral Arteries, Primarily by Interfering with the Flow Sensing Mechanisms
Authors: Koller Akos , Szénási Annamária , Szarka Nikolett , Buki Andras , Toth Peter 
Published: April 2020

Background

Traumatic brain injury (TBI) is a major health problem worldwide due to its high mortality (35–40%), and morbidity (headache, brain edema, cognitive, behavioral, and communicative disabilities). Previously we have shown that mechanotransductions of two hemodynamic factors, pressure and flow are importantly involved in the autoregulation of cerebral blood flow, which may become inefficient after TBI. Indeed, previously we have shown that TBI diminishes pressure‐induced myogenic constriction of middle cerebral arteries (MCA). In the present study we hypothesized that TBI effects also flow‐induced constrictor response of MCA.

Methods

TBI was induced in anaesthetized rat by Marmarou’s weight drop model, then MCA was isolated and transferred into pressure‐flow chamber. Inflow and outflow pressures were controlled and measured. The internal diameter was continuously measured by a videomicroscopy equipped with a microangiometer and recorded digitally by PowerLab system (AD Instruments). Data are mean±SEM.

Results

The active (242,2±6,1 μm) and passive (277,9±8,8) diameters (p<0.05) of isolated MCAs of control rats (n=39) indicate that a substantial myogenic tone developed in response to pressure (80 mmHg: Δ−35,7 ±2,7 μm, p<0.05). Arachidonic acid (AA) ‐ after initial dilations (+6±3 and +9±2,5 μm) ‐ elicited dose dependent constrictions (−9±2,1 and −20±3,2 μm) of MCA of control rats. Step increases in flow elicited gradual constrictions of MCA of control rats (from max.: 229,3±6,6 to 191±6 μm, Δ−38,3 ±0,6 μm, p<0.05), which was eliminated after TBI (from 227,3±14,1 to 227,4±13,3 μm). U46619, a thromboxane A2 (TXA2) / prostaglandin H2 (PGH2) receptor (TP receptor) agonist elicited similar constrictions of MCA of control and TBI rats (max.: Δ−66,1 ±0,7 μm vs. Δ−49 ±4 μm) rats, which were eliminated by SQ 29,548 a TP receptor antagonist. CYP‐450 metabolite 20‐HETE elicited similar constrictions of MCA in control (Δ−18 ±0,9 μm and TBI rats (Δ−15 ±0,1 μm) which were eliminated by HET0016, an inhibitor of CYP‐450. Paxilline (an inhibitor of potassium channel blocker) inhibited flow‐induced constrictions of MCA of control (max.: Δ−37,5 ±3 μm vs. max.: Δ−2,8 ±1 μm, p<0.05), whereas did not affect the diameters of MCA after TBI (max.: Δ−0,1 ±1,6 μm vs. Δ−2,5 ±3 μm).

Conclusions

These findings suggest that 1) flow‐induced constrictor response of MCA depends on AA‐metabolites acting on TP receptors, 2) constrictor responses to TP agonists remain intact after TBI, 3) thus TBI interferes primarily with the flow sensing mechanisms of the vascular wall, which 4) likely leads to diminished autoregulation of cerebral blood flow.

Support or Funding Information

Scientific Excellence Program 2019., at the University of Physical Education, Innovation and Technology Ministry, Hungary TUDFO/51757/2019‐ITM and Higher Education Institutional Excellence Program at Semmelweis University and the National Bionika Program ED_17‐1‐2017‐0009, Hungary, and the University of Pecs within the framework of the 5th. thematic programme, National Research Development and Innovation Office NKFI‐FK123798.