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Idiopathic intracranial hypertension (IIH) is a disease characterised by elevated intracranial pressure (ICP). The impact of straining and exercise on ICP regulation is poorly understood yet clinically relevant to IIH patient care. We sought to investigate the impact of Valsalva manoeuvres (VMs) and exercise on ICP and cerebrovascular haemodynamics in IIH. People with IIH were prospectively enrolled and had an intraparenchymal telemetric ICP sensor inserted. Three participants (age [mean ± standard deviation]: 40.3 ± 13.9 years) underwent continuous real-time ICP monitoring coupled with cerebrovascular haemodynamic assessments during VMs and moderate exercise. Participants had IIH with supine ICP measuring 15.3 ± 8.7 mmHg (20.8 ± 11.8 cm cerebrospinal fluid (CSF)) and sitting ICP measuring -4.2 ± 7.9 mmHg (-5.7 ± 10.7 cmCSF). During phase I of a VM ICP increased by 29.4 ± 13.5 mmHg (40.0 ± 18.4 cmCSF) but returned to baseline within 16 seconds from VM onset. The pattern of ICP changes during the VM phases was associated to that of changes in blood pressure, the middle cerebral artery blood velocity and prefrontal cortex haemodynamics. Exercise led to minimal effects on ICP. In conclusion, VM-induced changes in ICP were coupled to cerebrovascular haemodynamics and showed no sustained impact on ICP. Exercise did not lead to prolonged elevation of ICP. Those with IIH experiencing VMs (for example, during exercise and labour) may be reassured at the brief nature of the changes. Future research must look to corroborate the findings in a larger IIH cohort.
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Small extracellular vesicles (sEVs) are released from all cell types and participate in the intercellular exchange of proteins, lipids, metabolites and nucleic acids. Proteomic, flow cytometry and nanoparticle tracking analyses suggest sEVs are released into circulation with exercise. However, interpretation of these data may be influenced by sources of bias introduced by different analytical approaches. Seven healthy participants carried out a high intensity intermittent training (HIIT) cycle protocol consisting of 4 × 30 s at a work-rate corresponding to 200% of individual max power (watts) interspersed by 4.5 min of active recovery. EDTA-treated blood was collected before and immediately after the final effort. Platelet-poor (PPP) and platelet-free (PFP) plasma was derived by one or two centrifugal spins at 2500 g, respectively (15 min, room temperature). Platelets were counted on an automated haemocytometer. Plasma samples were assessed with the Exoview R100 platform, which immobilises sEVs expressing common tetraspanin markers CD9, CD63, CD81 and CD41a on microfluidic chips and with the aid of fluorescence imaging, counts their abundance at a single sEV resolution, importantly, without a pre-isolation step. There was a lower number of platelets in the PFP than PPP, which was associated with a lower number of CD9, CD63 and CD41a positive sEVs. HIIT induced an increase in fluorescence counts in CD9, CD63 and CD81 positive sEVs in both PPP and PFP. These data support the concept that sEVs are released into circulation with exercise. Furthermore, platelet-free plasma is the preferred, representative analyte to study sEV dynamics and phenotype during exercise. KEY POINTS: Small extracellular vesicles (sEV) are nano-sized particles containing protein, metabolites, lipid and RNA that can be transferred from cell to cell. Previous findings implicate that sEVs are released into circulation with exhaustive, aerobic exercise, but since there is no gold standard method to isolate sEVs, these findings may be subject to bias introduced by different approaches. Here, we use a novel method to immobilise and image sEVs, at single-vesicle resolution, to show sEVs are released into circulation with high intensity intermittent exercise. Since platelet depletion of plasma results in a reduction in sEVs, platelet-free plasma is the preferred analyte to examine sEV dynamics and phenotype in the context of exercise.
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Vesículas Extracelulares , Entrenamiento de Intervalos de Alta Intensidad , Humanos , Proteómica , Ejercicio Físico , Voluntarios SanosRESUMEN
The most common non-pharmacological intervention for both peripheral and cerebral vascular health is regular physical activity (e.g., exercise training), which improves function across a range of exercise intensities and modalities. Numerous non-exercising approaches have also been suggested to improved vascular function, including repeated ischemic preconditioning (IPC); heat therapy such as hot water bathing and sauna; and pneumatic compression. Chronic adaptive responses have been observed across a number of these approaches, yet the precise mechanisms that underlie these effects in humans are not fully understood. Acute increases in blood flow and circulating signalling factors that induce responses in endothelial function are likely to be key moderators driving these adaptations. While the impact on circulating factors and environmental mechanisms for adaptation may vary between approaches, in essence, they all centre around acutely elevating blood flow throughout the circulation and stimulating improved endothelium-dependent vascular function and ultimately vascular health. Here, we review our current understanding of the mechanisms driving endothelial adaptation to repeated exposure to elevated blood flow, and the interplay between this response and changes in circulating factors. In addition, we will consider the limitations in our current knowledge base and how these may be best addressed through the selection of more physiologically relevant experimental models and research. Ultimately, improving our understanding of the unique impact that non-pharmacological interventions have on the vasculature will allow us to develop superior strategies to tackle declining vascular function across the lifespan, prevent avoidable vascular-related disease, and alleviate dependency on drug-based interventions.
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Endotelio Vascular , Precondicionamiento Isquémico , Humanos , Endotelio Vascular/fisiología , Arteria Braquial/fisiología , Ejercicio Físico/fisiología , Adaptación Fisiológica/fisiologíaRESUMEN
PURPOSE: Red wine polyphenols (RWP) are plant-based molecules that have been extensively studied in relation to their protective effects on vascular health in both animals and humans. The aim of this review was to quantify and compare the efficacy of RWP and pure resveratrol on outcomes measures of vascular health and function in both animals and humans. METHODS: Comprehensive database searches were carried out through PubMed, Web of Science and OVID for randomised, placebo-controlled studies in both animals and humans. Meta-analyses were carried out on acute and chronic studies of RWP in humans, alongside sub-group analysis where possible. Risk-of-bias assessment was carried out for all included studies based on randomisation, allocation, blinding, outcome data reporting, and other biases. RESULTS: 48 animal and 37 human studies were included in data extraction following screening. Significant improvements in measures of blood pressure and vascular function following RWP were seen in 84% and 100% of animal studies, respectively. Human studies indicated significant improvements in systolic blood pressure overall (- 2.6 mmHg, 95% CI: [- 4.8, - 0.4]), with a greater improvement in pure-resveratrol studies alone (- 3.7 mmHg, 95% CI: [- 7.3, - 0.0]). No significant effects of RWP were seen in diastolic blood pressure or flow-mediated dilation (FMD) of the brachial artery. CONCLUSION: RWP have the potential to improve vascular health in at risk human populations, particularly in regard to lowering systolic blood pressure; however, such benefits are not as prevalent as those observed in animal models.
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Vitis , Vino , Animales , Presión Sanguínea , Humanos , Polifenoles/farmacología , ResveratrolRESUMEN
PURPOSE: This study investigated whether intermittent post-exercise sauna bathing across three-weeks endurance training improves exercise heat tolerance and exercise performance markers in temperate conditions, compared to endurance training alone. The subsidiary aim was to determine whether exercise-heat tolerance would further improve following 7-Weeks post-exercise sauna bathing. METHODS: Twenty middle-distance runners (13 female; mean ± SD, age 20 ± 2 years, [Formula: see text]O2max 56.1 ± 8.7 ml kg-1 min-1) performed a running heat tolerance test (30-min, 9 km h-1/2% gradient, 40 °C/40%RH; HTT) and temperate (18 °C) exercise tests (maximal aerobic capacity [[Formula: see text]O2max], speed at 4 mmol L-1 blood lactate concentration ([La-]) before (Pre) and following three-weeks (3-Weeks) normal training (CON; n = 8) or normal training with 28 ± 2 min post-exercise sauna bathing (101-108 °C, 5-10%RH) 3 ± 1 times per week (SAUNA; n = 12). Changes from Pre to 3-Weeks were compared between-groups using an analysis of co-variance. Six SAUNA participants continued the intervention for 7 weeks, completing an additional HTT (7-Weeks; data compared using a one-way repeated-measures analysis of variance). RESULTS: During the HTT, SAUNA reduced peak rectal temperature (Trec; - 0.2 °C), skin temperature (- 0.8 °C), and heart rate (- 11 beats min-1) more than CON at 3-Weeks compared to Pre (all p < 0.05). SAUNA also improved [Formula: see text]O2max (+ 0.27 L-1 min-1; p = 0.02) and speed at 4 mmol L-1 [La-] (+ 0.6 km h-1; p = 0.01) more than CON at 3-Weeks compared to Pre. Only peak Trec (- 0.1 °C; p = 0.03 decreased further from 3-Weeks to 7-Weeks in SAUNA (other physiological variables p > 0.05). CONCLUSIONS: Three-weeks post-exercise sauna bathing is an effective and pragmatic method of heat acclimation, and an effective ergogenic aid. Extending the intervention to seven weeks only marginally improved Trec.
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Tolerancia al Ejercicio/fisiología , Ejercicio Físico/fisiología , Resistencia Física/fisiología , Carrera/fisiología , Aclimatación/fisiología , Adulto , Rendimiento Atlético/fisiología , Baños/métodos , Regulación de la Temperatura Corporal/fisiología , Prueba de Esfuerzo/métodos , Femenino , Frecuencia Cardíaca/fisiología , Calor , Humanos , Masculino , Temperatura Cutánea/fisiología , Baño de Vapor/métodos , Termotolerancia/fisiología , Adulto JovenRESUMEN
Introduction: Mental stress has been identified as a trigger of cardiovascular events. A single episode of stress can induce acute impairments in endothelial function in healthy adults. Importantly, during stressful periods, individuals often resort to unhealthy behaviors, such as increased consumption of high-fat foods, which is also known to negatively impact endothelial function. Therefore, this study examined whether consumption of a high-fat meal would further exacerbate the negative effect of mental stress on vascular function. Methods: In a randomized, counterbalanced, cross- over, postprandial intervention study, 21 healthy males and females ingested a high-fat (56.5 g fat) or a low-fat (11.4 g fat) meal 1.5 h before an 8-min mental stress task (Paced-Auditory-Serial-Addition-Task, PASAT). Plasma triglyceride (TAG) concentration was assessed pre-and post-meal. Forearm blood flow (FBF), blood pressure (BP), and cardiovascular activity were assessed pre-meal at rest and post-meal at rest and during stress. Endothelial function, measured by brachial flow-mediated dilatation (FMD) was assessed pre-meal and 30 and 90 min following mental stress. Results: Plasma TAG concentration was significantly increased following the high-fat meal compared to the low-fat condition. Mental stress induced similar increases in peripheral vasodilation, BP, and cardiovascular activity, and impaired FMD 30 min post-stress, in both conditions. FMD remained significantly impaired 90 min following stress in the high-fat condition only, suggesting that consumption of fat attenuates the recovery of endothelial function following mental stress. Discussion: Given the prevalence of fat consumption during stressful periods among young adults, these findings have important implications for dietary choices to protect the vasculature during periods of stress.
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Mental stress has been associated with cardiovascular events and stroke, and has also been linked with poorer brain function, likely due to its impact on cerebral vasculature. During periods of stress, individuals often increase their consumption of unhealthy foods, especially high-fat foods. Both high-fat intake and mental stress are known to impair endothelial function, yet few studies have investigated the effects of fat consumption on cerebrovascular outcomes during periods of mental stress. Therefore, this study examined whether a high-fat breakfast prior to a mental stress task would alter cortical oxygenation and carotid blood flow in young healthy adults. In a randomised, counterbalanced, cross-over, postprandial intervention study, 21 healthy males and females ingested a high-fat (56.5 g fat) or a low-fat (11.4 g fat) breakfast 1.5 h before an 8-min mental stress task. Common carotid artery (CCA) diameter and blood flow were assessed at pre-meal baseline, 1 h 15 min post-meal at rest, and 10, 30, and 90 min following stress. Pre-frontal cortex (PFC) tissue oxygenation (near-infrared spectroscopy, NIRS) and cardiovascular activity were assessed post-meal at rest and during stress. Mental stress increased heart rate, systolic and diastolic blood pressure, and PFC tissue oxygenation. Importantly, the high-fat breakfast reduced the stress-induced increase in PFC tissue oxygenation, despite no differences in cardiovascular responses between high- and low-fat meals. Fat and stress had no effect on resting CCA blood flow, whilst CCA diameter increased following consumption of both meals. This is the first study to show that fat consumption may impair PFC perfusion during episodes of stress in young healthy adults. Given the prevalence of consuming high-fat foods during stressful periods, these findings have important implications for future research to explore the relationship between food choices and cerebral haemodynamics during mental stress.
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Encéfalo , Desayuno , Femenino , Masculino , Adulto , Humanos , Arteria Carótida Común , Dieta con Restricción de Grasas , Lóbulo FrontalRESUMEN
Background and aims: Sex differences in the rate and occurrence of cerebrovascular diseases (e.g., stroke) indicate a role for female sex hormones (i.e., oestrogen and progesterone) in cerebrovascular function and regulation. However, it remains unclear how cerebrovascular function differs between the sexes, and between distinct phases of the menstrual cycle. This study aimed to compare cerebrovascular-CO2 responsiveness in 1) females during the early follicular (EF), ovulatory (O) and mid-luteal (ML) phases of their menstrual cycle; and 2) males compared to females during phases of lower oestrogen (EF) and higher oestrogen (O). Methods: Eleven females (25 ± 5 years) complete experimental sessions in the EF (n = 11), O (n = 9) and ML (n = 11) phases of the menstrual cycle. Nine males (22 ± 3 years) completed two experimental sessions, approximately 2 weeks apart for comparison to females. Middle and posterior cerebral artery velocity (MCAv, PCAv) was measured at rest, during two stages of hypercapnia (2% and 5% CO2 inhalation) and hypocapnia (voluntary hyperventilation to an end-tidal CO2 of 30 and 24 mmHg). The linear slope of the cerebral blood velocity response to changes in end-tidal CO2 was calculated to measure cerebrovascular-CO2 responsiveness.. Results: In females, MCAv-CO2 responsiveness to hypocapnia was lower during EF (-.78 ± .45 cm/s/mmHg) when compared to the O phase (-1.17 ± .52 cm/s/mmHg; p < .05) and the ML phase (-1.30 ± .82; p < .05). MCAv-CO2 responsiveness to hypercapnia and hypo-to-hypercapnia, and PCAv-CO2 responsiveness across the CO2 range were similar between menstrual phases (p ≥ .20). MCAv-CO2 responsiveness to hypo-to hypercapnia was greater in females compared to males (3.12 ± .91 cm/s/mmHg vs. 2.31 ± .46 cm/s/mmHg; p = .03), irrespective of menstrual phase (EF or O). Conclusion: Females during O and ML phases have an enhanced vasoconstrictive capacity of the MCA compared to the EF phase. Additionally, biological sex differences can influence cerebrovascular-CO2 responsiveness, dependent on the insonated vessel.
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INTRODUCTION: Up to 40% of Parkinson's disease patients taking dopamine agonist medication develop impulse control behaviors which can have severe negative consequences. The current study aimed to utilize dopamine genetics to identify patients most at risk of developing these behaviors. METHODS: Demographic, clinical, and genetic data were obtained from the Parkinson's Progression Markers Initiative for de novo patients (n = 327), patients taking dopamine agonists (n = 146), and healthy controls (n = 160). Impulsive behaviors were identified using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease. A dopamine genetic risk score was calculated for each patient according to polymorphisms in genes coding for dopamine D1, D2 and D3 receptors, and catechol-O-methyltransferase. A higher score reflected higher central dopamine neurotransmission. RESULTS: Patients on agonists with a low dopamine genetic risk score were over 18 times more likely to have an impulsive behavior compared to higher scores (p = 0.04). The 38% of patients taking agonists who had at least one impulsive behavior were more likely to be male and report higher Unified Parkinson's Disease Rating Scale I&II scores. With increasing time on dopamine agonists (range 92-2283 days, mean 798 ± 565 standard deviation), only patients with a high dopamine genetic risk score showed an increase in number of impulsive behaviors (p = 0.033). Predictive effects of the gene score were not present in de novo or healthy control. CONCLUSIONS: A dopamine genetic risk score can identify patients most at risk of developing impulsive behaviors on dopamine agonist medication and predict how these behaviors may worsen over time.
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BACKGROUND: The purpose of this study was to investigate the effect of sex on the efficacy of intermittent post-exercise sauna bathing to induce heat acclimation and improve markers of temperate exercise performance in trained athletes. METHODS: Twenty-six trained runners (16 female; mean ± SD, age 19 ± 1 years, VÌO2max F: 52.6 ± 6.9 mLâ kg-1â min-1, M: 64.6 ± 2.4 mLâ kg-1â min-1) performed a running heat tolerance test (30 min, 9 kmâ h-1/2% gradient, 40 °C/40%RH; HTT) and temperate (18 °C) exercise tests (maximal aerobic capacity [VÌO2max] and lactate profile) pre and post 3 weeks of normal exercise training plus 29 ± 1 min post-exercise sauna bathing (101-108 °C) 3 ± 1 times per week. RESULTS: Females and males exhibited similar reductions (interactions p > 0.05) in peak rectal temperature (- 0.3 °C; p < 0.001), skin temperature (- 0.9 °C; p < 0.001) and heart rate (- 9 beats·min-1; p = 0.001) during the HTT at post- vs pre-intervention. Only females exhibited an increase in active sweat glands on the forearm (measured via modified iodine technique; F: + 57%, p < 0.001; M: + 1%, p = 0.47). Conversely, only males increased forearm blood flow (measured via venous occlusion plethysmography; F: + 31%, p = 0.61; M: + 123%; p < 0.001). Females and males showed similar (interactions p > 0.05) improvements in VÌO2max (+ 5%; p = 0.02) and running speed at 4 mmol·L-1 blood lactate concentration (+ 0.4 km·h-1; p = 0.001). CONCLUSIONS: Three weeks of post-exercise sauna bathing effectively induces heat acclimation in females and males, though possibly amid different thermoeffector adaptations. Post-exercise sauna bathing is also an effective ergogenic aid for both sexes.
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Sex differences in cerebrovascular disease rates indicate a possible role for ovarian sex steroid hormones in cerebrovascular function. To synthesise and identify knowledge gaps, a systematic review and meta-analysis was conducted to assess how ovarian sex steroid hormone changes across the lifespan affect cerebrovascular function in women. Three databases (EMBASE, MEDLINE and Web of Science) were systematically searched for studies on adult cerebrovascular function and ovarian sex steroid hormones. Forty-five studies met pre-defined inclusion criteria. Studied hormone groups included hormone replacement therapy (HRT; n = 17), pregnancy (n = 12), menstrual cycle (n = 7), menopause (n = 5), oral contraception (n = 2), and ovarian hyperstimulation (n = 2). Outcome measures included pulsatility index (PI), cerebral blood flow/velocity (CBF), resistance index (RI), cerebral autoregulation, and cerebrovascular reactivity. Meta-analysis was carried out on HRT studies. PI significantly decreased [-0.05, 95% CI: (-0.10, -0.01); p = 0.01] in post-menopausal women undergoing HRT compared to post-menopausal women who were not, though there was considerable heterogeneity (I 2 = 96.8%). No effects of HRT were seen in CBF (p = 0.24) or RI (p = 0.77). This review indicates that HRT improves PI in post-menopausal women. However, there remains insufficient evidence to determine how changing ovarian sex steroid hormone levels affects cerebrovascular function in women during other hormonal phases (e.g., pregnancy, oral contraception).
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[This corrects the article DOI: 10.3389/fphys.2020.609935.].
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The emergence of COVID-19 infection (caused by the SARS-CoV-2 virus) in Wuhan, China in the latter part of 2019 has, within a relatively short time, led to a global pandemic. Amidst the initial spread of SARS-CoV-2 across Asia, an epidemiologic trend emerged in relation to high altitude (HA) populations. Compared with the rest of Asia, SARS-CoV-2 exhibited attenuated rates of expansion with limited COVID-19 infection severity along the Tibetan plateau. These characteristics were soon evident in additional HA regions across Bolivia, central Ecuador, Nepal, Bhutan, and the Sichuan province of mainland China. This mini-review presents a discussion surrounding attributes of the HA environment, aspects of HA physiology, as well as, genetic variations among HA populations which may provide clues for this pattern of SARS-CoV-2 expansion and COVID-19 infection severity. Explanations are provided in the hypothetical, albeit relevant historical evidence is provided to create a foundation for future research.
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Altitud , Betacoronavirus , Infecciones por Coronavirus/epidemiología , Pandemias , Neumonía Viral/epidemiología , Enzima Convertidora de Angiotensina 2 , Bolivia/epidemiología , COVID-19 , China/epidemiología , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/metabolismo , Humanos , Nepal/epidemiología , Pandemias/estadística & datos numéricos , Peptidil-Dipeptidasa A/metabolismo , Neumonía Viral/diagnóstico , Neumonía Viral/metabolismo , SARS-CoV-2RESUMEN
Cocoa flavanols protect humans against vascular disease, as evidenced by improvements in peripheral endothelial function, likely through nitric oxide signalling. Emerging evidence also suggests that flavanol-rich diets protect against cognitive aging, but mechanisms remain elusive. In a randomized double-blind within-subject acute study in healthy young adults, we link these two lines of research by showing, for the first time, that flavanol intake leads to faster and greater brain oxygenation responses to hypercapnia, as well as higher performance only when cognitive demand is high. Individual difference analyses further show that participants who benefit from flavanols intake during hypercapnia are also those who do so in the cognitive challenge. These data support the hypothesis that similar vascular mechanisms underlie both the peripheral and cerebral effects of flavanols. They further show the importance of studies combining physiological and graded cognitive challenges in young adults to investigate the actions of dietary flavanols on brain function.
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Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Cognición/efectos de los fármacos , Flavonoles/administración & dosificación , Oxígeno/metabolismo , Adulto , Cacao , Corteza Cerebral/irrigación sanguínea , Circulación Cerebrovascular/efectos de los fármacos , Suplementos Dietéticos , Método Doble Ciego , Voluntarios Sanos , Humanos , Hipercapnia/dietoterapia , Hipercapnia/fisiopatología , Hipercapnia/psicología , Masculino , Persona de Mediana Edad , Consumo de Oxígeno/efectos de los fármacos , Oxihemoglobinas/metabolismo , Adulto JovenRESUMEN
This study examined acute cerebral hemodynamic and circulating neurotrophic factor responses to moderate intensity continuous exercise (MICT), guideline-based high intensity interval exercise (HIIT), and sprint interval exercise (SIT). We hypothesized that the pattern of middle cerebral artery velocity (MCAv) response would differ between interval and continuous exercise, with SIT inducing the smallest increase from rest, while increases in neurotrophic factors would be intensity-dependent. In a randomized crossover design, 24 healthy adults (nine females) performed three exercise protocols: (i) MICT (30 min), (ii) HIIT (4 × 4 min at 85% HRmax), and (iii) SIT (4 × 30 s supramaximal). MCAv significantly increased from rest across MICT (Δ13.1 ± 8.5 cmâ s-1, p < 0.001) and all bouts of HIIT (Δ15.2 ± 9.8 cmâ s-1, p < 0.001), but only for the initial bout of SIT (Δ17.3 ± 11.6 cmâ s-1, p < 0.001). Immediately following each interval bout, MCAv increased (i.e., rebounded) for the SIT (9-14% above rest, p ≤ 0.04), but not HIIT protocol. SIT alone induced significant elevations from rest to end-exercise in vascular endothelial growth factor (VEGF; Δ28 ± 36%, p = 0.017) and brain-derived neurotrophic factor (BDNF, Δ149% ± 162%, p < 0.001) and there were greater increases in lactate than in either other protocol (>5-fold greater in SIT, p < 0.001), alongside a small significant reduction at the end of active recovery in insulin-like growth factor 1 (IGF-1, Δ22 ± 21%, p = 0.002). In conclusion, while the nature of the response may differ, both guideline-based and sprint-based interval exercise have the potential to induce significant changes in factors linked to improved cerebrovascular and brain health.
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The optimal exercise intensity and modality for maximizing cerebral blood flow (CBF) and hence potential exposure to positive, hemodynamically derived cerebral adaptations is yet to be fully determined. This study compared CBF velocity responses between running and cycling across a range of exercise intensities. Twenty-six participants (12 females; age: 26 ± 8 years) completed four exercise sessions; two mode-specific maximal oxygen consumption (VO2max ) tests, followed by (order randomized) two incremental exercise protocols (3-min stages at 35%, 50%, 65%, 80%, 95% VO2max ). Continuous measures of middle cerebral artery velocity (MCAv), oxygen consumption, end-tidal CO2 (PET CO2 ), and heart rate were obtained. Modality-specific MCAv changes were observed for the whole group (interaction effect: p = .01). Exercise-induced increases in MCAvmean during cycling followed an inverted-U pattern, peaking at 65% VO2max (Δ12 ± 7 cm/s from rest), whereas MCAvmean during running increased linearly up to 95% VO2max (change from rest: Δ12 ± 13 vs. Δ7 ± 8 cm/s for running vs. cycling at 95% VO2max ; p = .01). In contrast, both modalities had an inverted-U pattern for PET CO2 changes, although peaked at different intensities (running: 50% VO2max , Δ6 ± 2 mmHg; cycling: 65% VO2max , Δ7 ± 2 mmHg; interaction effect: p = .01). Further subgroup analysis revealed that the running-specific linear MCAvmean response was fitness dependent (Fitness*modality*intensity interaction effect: p = .04). Above 65% VO2max , fitter participants (n = 16; male > 45 mL/min/kg and female > 40 mL/min/kg) increased MCAvmean up to 95% VO2max , whereas in unfit participants (n = 7, male < mL/min/kg and female < 35 mL/min/kg) MCAvmean returned toward resting values. Findings demonstrate that modality- and fitness-specific profiles for MCAvmean are seen at exercise intensities exceeding 65% VO2max .