Previous studies have identified the dorsolateral prefrontal cortex (dlPFC) as a core region in cognitive emotional regulation. Transcranial direct current stimulations of the dlPFC (tDCS) and heart-rate variability biofeedback (BFB) are known to regulate emotional processes. However, the effect of these interventions applied either alone or concomitantly during an anticipatory stress remains unexplored. The study investigated the effect of anodal tDCS and BFB, alone or combined, on psychophysiological stress responses and cognitive functioning. Following a stress anticipation induction, 80 participants were randomized into four groups and subjected to a 15-min intervention: neutral video viewing (ctrl), left dlPFC anodal tDCS (tdcs), heart-rate variability biofeedback (bfb), or a combined treatment (bfb + tdcs). Participants were then immediately confronted with the stressor, which was followed by an assessment of executive functions. Psychophysiological stress responses were assessed throughout the experiment (heart rate, heart-rate variability, salivary cortisol). The tdcs did not modulate stress responses. Compared with both ctrl and tdcs interventions, bfb reduced physiological stress and improved executive functions after the stressor. The main finding revealed that bfb + tdcs was the most effective intervention, yielding greater reduction in psychological and physiological stress responses than bfb. Combining preventive tDCS with BFB is a relevant interventional approach to reduce psychophysiological stress responses, hence offering a new and non-invasive treatment of stress-related disorders. Biofeedback may be particularly useful for preparing for an important stressful event when performance is decisive.

High-intensity interval training (HIIT) and linseed oil (LO) supplementation are effective strategies to reduce obesity-induced oxidative stress. Our aim was to determine whether the HIIT + LO combination prevents obesity-induced oxidative stress in high fat diet (HFD)-fed rats. HFD-fed 8-week-old, male, Wistar rats were subdivided in four groups: HFD, LO (2% of sunflower oil replaced with 2% of LO in the HFD), HIIT (4 days/week for 12 weeks), and HIIT + LO. Wistar rats fed a low-fat diet (LFD) were used as controls. Epididymal and subcutaneous adipose tissue, gastrocnemius muscle, liver, and plasma samples were collected to measure oxidative stress markers (AOPP, oxLDL), antioxidant (SOD, CAT, and GPx activities) and pro-oxidant (NOx and XO) enzyme activities. Compared with the LFD, the HFD altered the pro/antioxidant status in different tissues (increase of AOPP, oxLDL, SOD and catalase activities in plasma, and SOD activity increase in liver and decrease in adipose tissues) but not in gastrocnemius. LO upregulated CAT activity and decreased NOx in liver. HIIT alleviated HFD negative effects in liver by reducing SOD and NOx activities. Moreover, the HIIT + LO combination potentiated SOD activity upregulation in subcutaneous tissue. HIIT and LO supplementation have independent beneficial effects on the pro/antioxidant balance. Their association promotes SOD activity in subcutaneous adipose tissue.

Background: Carotid atherosclerotic plaques remain silent until their rupture, which may lead to detrimental ischemic events such as strokes. This is due, in part, to intraplaque hemorrhages (IPH) and the resulting inflammatory processes, which may promote carotid plaque vulnerability. Currently, the benefits of carotid endarterectomy remain unclear for asymptomatic patients. Interestingly, the completion of physical activity (PA) may have beneficial effects; however, the paucity of current data warrants robust longitudinal interventions. We therefore aim to study the effects of a 6-month longitudinal personalized home-based PA program on IPH, biological, and inflammatory markers in asymptomatic stroke patients. Methods: Eighty patients (≥ 18 years old) will be recruited for the Physical Activity and Carotid Atherosclerotic Plaque Hemorrhage (PACAPh) clinical trial from the Hospices Civils de Lyon. Patients will be eligible if they present with carotid stenosis ≥ 50% and are asymptomatic from any ischemic events for at least 6 months. Recruited patients will be randomized into either a PA or a control group, and assessed at baseline and after 6 months. At both time points, all patients will be assessed using magnetic resonance imaging to assess IPH, blood sampling to measure inflammatory markers and monocytic phenotyping, PA and sedentary behavior questionnaires, 6-min walking test, and maximal isometric quadricep contraction test. The randomized PA intervention will consist of reaching a daily walking step goal individually tailored to each patient. Steps will be collected using a wirelessly connected wristband. The number of steps completed by individuals in the PA group will be re-evaluated bimonthly to encourage walking habits. Discussion: The PACAPh study is the first of its kind representing a feasible, easily accessible therapeutic strategy for asymptomatic stroke patients. We hypothesize that the personalized home-based PA program will reduce IPH and modulate inflammatory and biological parameters in patients presenting with carotid plaques. If the results of the PACAPh study prove to be beneficial on such health parameters, the implementation of such kind of intervention in the daily treatment of these patients would be an advantageous and cost-effective practice to adopt globally. Trial registration: This study has been approved by the National Ethics Committee (IDRCB:2019-A01543-54/SI:19.06.21.40640). ClinicalTrials.gov NCT04053166

Atherosclerosis is associated with low-grade inflammation involving circulating monocytes. It has been shown that the levels of intermediate pro-inflammatory monocytes are associated with cardiovascular mortality and risk of ischemic stroke. It also has been shown that physical activity (PA) decreases inflammation markers, incidence of strokes, and mortality. In this cross-sectional study, we tested the effect of PA on circulating monocytes phenotype rate. A total of 29 patients with a carotid stenosis > 50% were recruited. Levels of physical activity (MET.min/week) were measured by the GPAQ questionnaire, arterial samples of blood were collected to analyze monocyte phenotype (classical, intermediate and non-classical) assessed by flow cytometry, and venous blood samples were used to dose antioxidant activity and oxidative damage. Antioxidant capacity was reduced and oxidative damage increased in patients. There was a significant decrease in the percentage of classical and intermediate monocytes in moderately active patients as compared with non-active and highly active patients. Inversely, the rate of non-classical monocytes increased in moderately active patients. Intense PA appears to blunt the beneficial effects of moderate PA. Our study also suggests that PA could be beneficial in such patients by reducing the rate of intermediate monocytes known to predict the risk of ischemic stroke and by increasing the non-classical monocytes involved in lesions’ healing. Nevertheless, a longitudinal study would be necessary to confirm this hypothesis.

Management of asymptomatic patients with carotid atherosclerotic plaque is still debated. Intraplaque haemorrhage measured by magnetic resonance imaging is the best in-vivo indicator of plaque instability and ischaemic risk. A cross-sectional study reported that physical activity was associated with lower prevalence of carotid intraplaque haemorrhage. The aim of this trial was to determine the influence of a physical activity intervention on plaque instability in asymptomatic patients with carotid stenosis. Physical Activity and Carotid Atherosclerotic Plaque haemorrhage is a randomized clinical trial (ID-RCB:2019-A01543-54/SI:19.06.21.40640; registered on clinicaltrials.gov NCT04053166). Patients were enrolled at University Hospital of Lyon, France, from December 2019 to March 2022. Fifty-six asymptomatic patients with carotid artery stenosis ≥50% NASCET were included and randomized 1:1 in an interventional physical activity arm or a control arm. The interventional arm underwent 6 months of an individualized home-based physical activity program, while the control arm followed usual care. The main outcome is the variation of the intraplaque haemorrhage score measured with high-resolution magnetic resonance imaging of the carotid plaque. All data were analysed with an intention to treat. Investigators were blinded from grouping. Out of 52 patients participating in the trial, 26 were allocated in each arm. The intraplaque haemorrhage score was significantly reduced over time in the physical activity arm (estimate difference: −0.32 ± 0.15, [95% CI −0.63 to −0.01], p = 0.04). The physical activity arm had increased daily step counts at the end of the 6-month intervention compared to the control arm (1843 ± 758, [CI95% 313–3373], p = 0.02). This trial demonstrates that an individualized home-based physical activity intervention could reduce the severity of intraplaque haemorrhage detected by magnetic resonance imaging and that it is feasible in asymptomatic patients with carotid atherosclerotic plaque. These results suggest that this type of moderate-intensity physical activity could be included in this population to the best medical treatment. This study was funded by the 10.13039/501100003100 Fédération Française de Cardiologie and Nouvelle Société Francophone d’Athérosclérose .

Up to 25 % of ischemic strokes are the consequence of a ruptured vulnerable carotid atherosclerotic plaque. Circulating pro-inflammatory classical and intermediate monocytes are known predictors of ischemic events and cardiovascular death. Interestingly, chronic physical activity can decrease inflammation, and is thereby associated with a reduction in pro-inflammatory monocytes. In a randomized, controlled and monocentric trial, we recruited 56 patients (71 ± 8 years old) with asymptomatic carotid stenosis of ≥50 % who were ineligible for carotid endarterectomy. Blood analyses were completed to assess the phenotype of monocytes, as well as a multiplex assay and colorimetric assay for cytokines concentration and redox status, respectively. Classical monocyte count was increased in the control arm, while it remained stable in response to the physical activity intervention (-5215 ± 2307, [95 %CI -9878 to -551], p = 0.03). Moreover, the expression of most of pro-inflammatory cytokines was down-regulated in response to the physical activity intervention, while it was increased in the control arm. The stabilization of classical monocytes and down-regulation of the expression of pro-inflammatory cytokines in response to the physical activity intervention suggest that chronic physical activity alleviate the pro-inflammatory state, and might thereby reduce carotid plaque vulnerability and the subsequent risk of ischemic events. These results highlight that home-based physical activity intervention is an efficient clinical care that induce biological changes in carotid atherosclerotic patients.