The larger intracranial conduit vessels contribute to the total cerebral vascular resistance, and understanding their vasoreactivity to physiological stimuli is required when attempting to understand regional brain perfusion. Reactivity of the larger cerebral conduit arteries remains understudied due to a need for improved imaging methods to simultaneously assess these vessels in a single stimulus. We characterized reactivity of basal intracranial conduit arteries (basilar, right and left posterior, middle and anterior cerebral arteries) and the right and left internal carotid arteries, to manipulations in end-tidal CO (PetCO). Cross-sectional area changes (%CSA) were evaluated from high-resolution (0.5 mm isotropic) images collected at 7 T using a T1-weighted 3D SPACE pulse sequence, providing high contrast between vessel lumen and surrounding tissue. Cerebrovascular reactivity was calculated as %CSA/ΔPetCO in eight healthy individuals (18-23 years) during normocapnia (41 ± 4 mmHg), hypercapnia (48 ± 4 mmHg; breathing 5% CO, balance oxygen), and hypocapnia (31 ± 8 mmHg; via hyperventilation). Reactivity to hypercapnia ranged from 0.8%/mmHg in the right internal carotid artery to 2.7%/mmHg in the left anterior cerebral artery. During hypocapnia, vasoconstriction ranged from 0.9%/mmHg in the basilar artery to 2.6%/mmHg in the right posterior cerebral artery. Heterogeneous cerebrovascular reactivity to hypercapnia and hypocapnia was characterized across basal intracranial conduit and internal carotid arteries.

Acute liver failure was induced in rats by successive administrations of thioacetamide over 3 days. At progressing stages of hepatic encephalopathy (HE), brains were fixed with microwave irradiation for analysis of metabolite levels or with formaldehyde for histopathological analysis. Metabolite levels were determined using 1H-nuclear magnetic resonance spectroscopy of perchloric acid extracts of the frontal cortex, parietal or occipital cortex, hippocampus, striatum, brain stem, and cerebellum. After thioacetamide treatment, thioacetamide and its metabolites were detected in the brains at levels that did not correlate with the stage of HE. No changes were observed in the levels of N-acetylaspartate, alanine, gamma-aminobutyric acid, aspartate, or inositol in any brain region after thioacetamide treatment. HE was accompanied by elevated glutamine, glucose, and lactate throughout the brain. At all stages of HE, taurine was decreased in the neocortex and hippocampus, and glutamate and choline compounds were decreased in the frontal cortex. None of the metabolite changes showed progression with the stage of HE. Progressing HE was accompanied by increasing neuronal injury in layer III of the neocortex, in the Purkinje cells of the cerebellum, and in the hippocampus, particularly in the CA4 sector. The similarity of this distribution of injury to that associated with excitotoxic injury suggests that metabolic abnormalities after acute hepatic failure may give rise to adverse effects at excitatory (glutamatergic) neuronal receptors, leading to neuronal injury and clinical symptoms of progressing encephalopathy in this model. However, neuronal injury and the presence of thioacetamide and its metabolites in the brain raise questions about the validity of thioacetamide-induced liver failure as a model for clinical HE.

The current study demonstrates that the sympathetic neural recruitment patterns observed during chemoreflex activation induced by rebreathing or apnea are restrained and/or inhibited by the act of ventilation per se, despite similar, or even greater, levels of severe chemoreflex stress. Therefore, ventilation modulates not only the timing of sympathetic bursts but also the within-burst axonal recruitment normally observed during progressive chemoreflex stress.

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Key points Cognitive function depends on adequate cerebrovascular perfusion and control. However, it is unknown whether acutely‐reduced cerebral blood flow (CBF) impairs cognition in healthy adults. In the present study, we used a placebo‐controlled, single‐blinded, randomized cross‐over design to test the hypothesis that acutely‐reduced CBF (using a pharmacological aid; indomethacin) would impair cognition in young and older healthy adults. At baseline, older adults had lower cognitive performance and CBF, but similar cerebrovascular reactivity to CO2 and dynamic cerebral autoregulation compared to young adults. In both young and older adults, cognitive performance on a mental switching task was slightly (7%) reduced after indomethacin, but not significantly associated with reductions in CBF (∼31%). These results indicate that cognitive performance is broadly resilient against a ∼31% reduction in CBF per se in healthy young and older adults. Abstract Cognitive function depends on adequate cerebrovascular perfusion and control. However, it is unknown whether acutely‐reduced cerebral blood flow (CBF) impairs cognition in healthy adults. Using a placebo‐controlled, single‐blinded, randomized cross‐over design, we tested the hypothesis that acutely‐reduced CBF (using indomethacin [1.2 mg kg–1 oral dose]) would impair cognition in young (n = 13; 25 ± 4 years) and older (n = 12; 58 ± 6 years) healthy adults. CBF and cerebrovascular control were measured using middle cerebral artery blood velocity (MCAvmean) and its reactivity to hypercapnia (CVRHYPER) and hypocapnia (CVRHYPO), respectively. Cognitive function was assessed using a computerized battery including response time tasks. Baseline comparisons revealed that older adults had 14% lower MCAvmean and 15% lower cognitive performance (all P ≤ 0.048), but not lower CVRHYPER/HYPO (P ≥ 0.26). Linear and rank‐based mixed models revealed that indomethacin decreased MCAvmean by 31% (95% confidence interval = –35 to –26), CVRHYPER by 68% [interquartile range (IQR) = –94 to –44] and CVRHYPO by 50% (IQR = –83 to –33) (treatment‐effect; all P < 0.01), regardless of age. Baseline CVRHYPER/HYPO values were strongly associated with their indomethacin‐induced reductions (r = 0.70 to 0.89, P < 0.01). Mental switching performance was impaired 7% (IQR = 0–19) after indomethacin (P = 0.04), but not significantly associated with reductions in MCAvmean (Young: rho = –0.31, P = 0.30; Older: rho = 0.06, P = 0.86). In conclusion, indomethacin reduced MCAvmean and impaired cognition slightly; however, no clear association was evident in younger or older adults. Older adults had poorer cognition and lower MCAvmean, but similar CVRHYPER/HYPO.

Both acute and regular exercise influence vascular and cognitive function. Upright aquatic exercise increases mean middle cerebral artery blood velocity (MCAvmean) and has been suggested as favorable for cerebrovascular adaptations. However, MCAvmean has not been reported during swimming. Thus, we examined the cerebrovascular and cognitive effects of swimming. Ten land‐based athletes (22 ± 5 years) and eight swimmers (19 ± 1 years) completed three cognitive tasks and four conditions that were used to independently and collectively delineate the swimming‐related factors (i.e., posture, immersion, CO2 retention [end‐tidal CO2; PETCO2], and motor involvement). Measurements of MCAvmean and PETCO2 were taken throughout each condition. Prone posture increased MCAvmean by 11% (P < 0.01 vs. upright land). Water immersion independently increased MCAvmean when upright (12%; P < 0.01) but not prone (P = 0.76). The consequent rise in PETCO2 during head‐out, breast‐stroke swimming (50% heart rate range) independently increased MCAvmean by 14% (P < 0.01), while the motor involvement of swimming per se did not significantly change MCAvmean (P = 0.32). While accounting for sex, swimmers had ~17% lower MCAvmean during all rest conditions (P ≤ 0.05). However, in a subset of participants, both groups had similar internal carotid artery diameters (P = 0.99) and velocities (P = 0.97). Water immersion per se did not alter cognition (P ≥ 0.15), but 20 min of moderate‐intensity swimming improved visuomotor performance by 4% (P = 0.03), regardless of athlete group (P = 0.12). In conclusion, breast‐stroke swimming increased MCAvmean mostly due to postural and PETCO2 effects, with minimal contributions from water immersion or motor activity. Lastly, swimming improved cognitive functioning acutely, regardless of athlete group. Future research should explore the chronic effects of swimming on cerebrovascular function and cognition, particularly in aging.

In this study, we examined the effects of acute mental stress on cerebrovascular function.Sixteen participants (aged 23 ± 4 years; five female) were exposed to low and high mental stress using simple arithmetic (counting backwards from 1000) and more complex arithmetic (serial subtraction of 13 from a rapidly changing four-digit number), respectively. During consecutive conditions of baseline, low stress and high stress, end-tidal partial pressure of CO 2 (P ET,CO 2 ) was recorded at normocapnia (37 ± 3 mmHg) and clamped at two elevated levels (P < 0.01): 41 ± 1 and 46 ± 1 mmHg. Mean right middle cerebral artery blood velocity (MCAv mean ; transcranial Doppler ultrasound), right prefrontal cortex haemodynamics (near-infrared spectroscopy) and mean arterial blood pressure (MAP; finger photoplethysmography) were measured continuously.Cerebrovascular hypercapnic reactivity (ΔMCAv mean /ΔP ET,CO 2 ), cerebrovascular conductance (CVC; MCAv mean /MAP), CVC CO 2 reactivity (ΔCVC/ΔP ET,CO 2 ) and total peripheral resistance (MAP/cardiac output) were calculated. Acute high mental stress increased MCAv mean by 7 ± 7%, and more so at higher P ET,CO 2 (32 ± 10%; interaction, P = 0.03), illustrating increased sensitivity to CO 2 (i.e. its major regulator). High mental stress also increased MAP (17 ± 9%; P ≤ 0.01), coinciding with increased near-infrared spectroscopy-derived prefrontal haemoglobin volume and saturation measures. High mental stress elevated both cerebrovascular hypercapnic and conductance reactivities (main effect of stress, P ≤ 0.04). These findings indicate that the cerebrovascular response to acute high mental stress results in a coordinated regulation between multiple processes.

The endothelin-B (ETB) receptor mediates vasodilation in young women, an effect lost following menopause. It is unclear whether these alterations are due to aging or changes in estradiol (E2). During endogenous hormone suppression (GnRH antagonist), blockade of ETB receptors enhanced cutaneous microvascular vasodilation. However, during E2 administration, blockade of ETB receptors attenuated vasodilation, indicating that the ETB receptor mediates dilation in the presence of E2. In young women, ETB receptors mediate vasodilation in the presence of E2, an effect that is lost when E2 is suppressed.