Characterising the protective vasodilatory effects of hypobaric hypoxia on the neurovascular coupling response

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Neurovascular coupling (NVC) is the link between local neuronal activity and regional cerebral blood flow. High altitude (HA) ascent induces acute hypoxic vasodilation of vasculature, with associated changes in CO 2 acid-base status. We aimed to characterise effects (a) removal HA-induced (b) rapid residency at HA on NVC responses. In twelve healthy participants (7 M/5F), arterial gases were measured baseline (1130 m) days two (<24 h HA) nine (post-acclimatisation) 3800 m. Acute gas challenges performed using end-tidal forcing, normoxia isocapnic hypoxia 1130 m poikilocapnic hyperoxia Posterior artery velocity (PCAv) was transcranial Doppler ultrasound each condition time-point. assessed via a standardized 30 s intermittent strobe light visual stimulus (VS), quantified as peak mean change from PCAv. No significant differences observed for any metric across all conditions time points. Our results reveal remarkable stability response following

Language: Английский

---

Control of Cerebral Blood Flow by Blood Gases

Frontiers in Physiology, Journal Year: 2021, Volume and Issue: 12

Published: Feb. 18, 2021

Cerebrovascular reactivity can be measured as the cerebrovascular flow response to a hypercapnic challenge. The many faceted responses of cerebral blood combinations gas challenges are mediated by its vasculature’s smooth muscle and comprehensively described simple mathematical model. model accounts for during hypoxia, anemia, hypocapnia, hypercapnia. main hypothetical basis is that these various challenges, singly or in combination, act via common regulatory pathway: regulation intracellular hydrogen ion concentration. This achieved membrane transport strongly dissociated ions control their concentrations. assumes vasoconstriction vasodilation hence flow, proportional Model predictions hypercapnia match form observed responses, providing some confidence theories on which based have merit.

Language: Английский

---

Neuronal nitric oxide synthase regulates regional brain perfusion in healthy humans

Cardiovascular Research, Journal Year: 2021, Volume and Issue: 118(5), P. 1321 - 1329

Published: April 28, 2021

Abstract Aims Neuronal nitric oxide synthase (nNOS) is highly expressed within the cardiovascular and nervous systems. Studies in genetically modified mice suggest roles brain blood flow regulation while dysfunctional nNOS signalling implicated cerebrovascular ischaemia migraine. Previous human studies have investigated effects of non-selective NOS inhibition but there has been no direct investigation role regulation. We hypothesized that tonic would result global or localized changes cerebral (CBF), as well functional connectivity. Methods results acute a selective inhibitor, S-methyl-L-thiocitrulline (SMTC), on CBF connectivity healthy volunteers (n = 19). performed randomized, placebo-controlled, crossover study with either intravenous SMTC placebo, using magnetic resonance imaging protocols arterial spin labelling resting state neuroimaging. infusion induced an ∼4% decrease [−2.3 (−0.3, −4.2) mL/100g/min, mean (95% confidence interval, CI), P 0.02]. In whole-brain voxel-wise factorial-design comparison maps, we identified regional right hippocampus parahippocampal gyrus following vs. placebo (2921 voxels; T 7.0; x 36; y −32; z −12; &lt; 0.001). This was accompanied by to left superior parietal lobule (484 5.02; −14; −56; 74; 0.009). These analyses adjusted for modest pressure compared [+8.7 mmHg (+1.8, +15.6), 0.009]. Conclusions data fundamental physiological regulating hippocampus. Our findings relevance perfusion health disease.

Language: Английский

---

Allyl Isothiocianate Induces Ca2+ Signals and Nitric Oxide Release by Inducing Reactive Oxygen Species Production in the Human Cerebrovascular Endothelial Cell Line hCMEC/D3

Cells, Journal Year: 2023, Volume and Issue: 12(13), P. 1732 - 1732

Published: June 27, 2023

Nitric oxide (NO) represents a crucial mediator to regulate cerebral blood flow (CBF) in the human brain both under basal conditions and response somatosensory stimulation. An increase intracellular Ca2+ concentrations ([Ca2+]i) stimulates endothelial NO synthase produce cerebrovascular cells. Therefore, targeting ion channel machinery could represent promising strategy rescue signalling traumatic injury neurodegenerative disorders. Allyl isothiocyanate (AITC), major active constituent of cruciferous vegetables, was found CBF non-human preclinical models, but it is still unknown whether release capillary In present investigation, we showed that AITC evoked Ca2+-dependent cell line, hCMEC/D3. The shaped by intra- extracellular sources, although insensitive pharmacological blockade transient receptor potential ankyrin 1, which regarded be among main molecular targets AITC. accord, failed induce transmembrane currents or elicit membrane hyperpolarization, NS309, selective opener small- intermediate-conductance Ca2+-activated K+ channels, induced significant hyperpolarization. AITC-evoked signal triggered production cytosolic, not mitochondrial, reactive oxygen species (ROS), supported store-operated entry (SOCE). Conversely, did require mobilization from endoplasmic reticulum, lysosomes mitochondria. However, manipulation revealed AITC-dependent ROS generation inhibited plasma Ca2+-ATPase (PMCA) activity, thereby attenuating removal across resulting sustained [Ca2+]i. driven required ROS-dependent inhibition PMCA activity. These data suggest exploited restore disorders feature neurovascular dysfunction.

Language: Английский

---

The Role of NRF2 in Cerebrovascular Protection: Implications for Vascular Cognitive Impairment and Dementia (VCID)

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3833 - 3833

Published: March 29, 2024

Vascular cognitive impairment and dementia (VCID) represents a broad spectrum of decline secondary to cerebral vascular aging injury. It is the second most common type dementia, prevalence continues increase. Nuclear factor erythroid 2-related 2 (NRF2) enriched in vasculature has diverse roles metabolic balance, mitochondrial stabilization, redox anti-inflammation. In this review, we first briefly introduce cerebrovascular VCID NRF2 pathway. We then extensively discuss effects activation components such as endothelial cells, smooth muscle pericytes, perivascular macrophages. Finally, summarize clinical potential activators VCID.

Language: Английский

---