Paradoxical symptomatic cerebral blood flow decreases after combined revascularization surgery for patients with pediatric moyamoya disease: illustrative case

BACKGROUND Transient neurological deficits (TNDs) develop after cerebral revascularization in patients with moyamoya disease (MMD). The authors report a rare pediatric MMD case with extensive decreased cerebral blood flow (CBF) and prolonged TNDs after combined revascularization. OBSERVATIONS A 9-year-old boy presented with transient left upper limb weakness, and MMD was diagnosed. A right-sided combined surgery was performed. Two years after the surgery, frequent but transient facial (right-sided) and upper limb weakness appeared. The left internal carotid artery terminal stenosis had progressed. Therefore, a left combined revascularization was performed. The patient’s motor aphasia and right upper limb weakness persisted for approximately 10 days after surgery. Magnetic resonance angiography showed that the direct bypass was patent, but extensive decreases in left CBF were observed using single photon emission tomography. With adequate fluid therapy and blood pressure control, the neurological symptoms eventually disappeared, and CBF improved. LESSONS The environment of cerebral hemodynamics is heterogeneous after cerebral revascularization for MMD, and the exact mechanism of CBF decreases was not identified. TNDs are significantly associated with the onset of stroke during the early postoperative period. Therefore, appropriate treatment is desired after determining complex cerebral hemodynamics using CBF studies.

Insulin sensitizes neural and vascular TRPV1 receptors in the trigeminovascular system

Background Clinical observations suggest that hyperinsulinemia and insulin resistance can be associated with migraine headache. In the present study we examined the effect of insulin on transient receptor potential vanilloid 1 (TRPV1) receptor-dependent meningeal nociceptor functions in rats. Methods The effects of insulin on the TRPV1 receptor stimulation-induced release of calcitonin gene related peptide (CGRP) from trigeminal afferents and changes in meningeal blood flow were studied. Colocalization of the insulin receptor, the TRPV1 receptor and CGRP was also analyzed in trigeminal ganglion neurons. Results Insulin induced release of CGRP from meningeal afferents and consequent increases in dural blood flow through the activation of TRPV1 receptors of trigeminal afferents. Insulin sensitized both neural and vascular TRPV1 receptors making them more susceptible to the receptor agonist capsaicin. Immunohistochemistry revealed colocalization of the insulin receptor with the TRPV1 receptor and CGRP in a significant proportion of trigeminal ganglion neurons. Conclusions Insulin may activate or sensitize meningeal nociceptors that may lead to enhanced headache susceptibility in persons with increased plasma insulin concentration.

Role of anatomical location, cellular phenotype and perfusion of adipose tissue in intermediary metabolism: A narrative review

It is well-established that adipose tissue accumulation is associated with insulin resistance through multiple mechanisms. One major metabolic link is the classical Randle cycle: enhanced release of free fatty acids (FFA) from hydrolysis of adipose tissue triglycerides impedes insulin-mediated glucose uptake in muscle tissues. Less well studied are the different routes of this communication. First, white adipose tissue depots may be regionally distant from muscle (i.e., gluteal fat and diaphragm muscle) or contiguous to muscle but separated by a fascia (Scarpa’s fascia in the abdomen, fascia lata in the thigh). In this case, released FFA outflow through the venous drainage and merge into arterial plasma to be transported to muscle tissues. Next, cytosolic triglycerides can directly, i.e., within the cell, provide FFA to myocytes (but also pancreatic ß-cells, renal tubular cells, etc.). Finally, adipocyte layers or lumps may be adjacent to, but not anatomically segregated, from muscle, as is typically the case for epicardial fat and cardiomyocytes. As regulation of these three main delivery paths is different, their separate contribution to substrate competition at the whole-body level is uncertain. Another important link between fat and muscle is vascular. In the resting state, blood flow is generally higher in adipose tissue than in muscle. In the insulinized state, fat blood flow is directly related to whole-body insulin resistance whereas muscle blood flow is not; consequently, fractional (i.e., flow-adjusted) glucose uptake is stimulated in muscle but not fat. Thus, reduced blood supply is a major factor for the impairment of in vivo insulin-mediated glucose uptake in both subcutaneous and visceral fat. In contrast, the insulin resistance of glucose uptake in resting skeletal muscle is predominantly a cellular defect.

Blood flow restriction with different load levels in patients with knee osteoarthritis: protocol of a randomized controlled trial

Background The effectiveness of blood flow restriction training (BFR) in elderly with knee osteoarthritis (OA) is comparable to performing high-intensity protocols (70 to 80% of 1 RM [repetition maximum]) that are known to be effective for improving the muscle strength of knee extensors, with the advantage of generating less particular rating of perceived exertion and pain immediately after training. However, despite being a promising alternative, little is known about the best way to apply the BFR, such as level of pressure and combination or not with other therapeutic modalities. The purpose of this study is to evaluate whether different levels of blood flow restriction with low load (BFR + LL) and no load (BFR + rest) are non-inferior to high-intensity resistance exercise (HIRE+BFRplacebo) for pain reduction in patients with knee OA. Methods/design This clinical trial is a non-inferiority, five-arm, randomized, active-controlled, single trial which will be carried out in 165 patients of both sexes with knee OA, aged 50 years and older. Participants will be randomly allocated into 5 exercise groups (40% of BFR + LL; 80% of BFR + LL; 40% of BFR + rest; 80% BFR + rest, and HIRE+BFR placebo). A mixed linear model will be used to examine the effect of group-by-time interaction on pain intensity on the WOMAC subscale (primary outcome) and on disease severity, physical functional data, balance data, quality of life, global perceived effect scale, and muscle strength (secondary outcomes). Participants will be analyzed for intention-to-treat, and the statistical assessor blinded to the groups. The collection of outcomes 72 h after completion of the 16 weeks of interventions will be the primary measurement point. Follow-up secondary timepoints will be collected at 20, 28, 40, 52, and 64 weeks after the end of interventions, except for pain during the training, which will be measured immediately at the end of each session. Only the comparison of the primary outcome between the HIRE group with each BFR group will be analyzed in the non-inferiority framework, the other comparisons between the BFR groups for the primary outcome, and all secondary outcomes will be interpreted in the superiority framework. Discussion The results of this clinical trial can point out more clearly to ways to optimize the BFR training with the minimum of pain immediately after training, which will allow the offer of an effective and more adherent strengthening training to patients with knee OA. Trial registration Registro Brasileiro de Ensaios Clínicos, RBR-93rx9q. Registered on 23 July 2020. Version 1.0.

Why Does Vascular Access Dysfunction Occur despite Brachial Artery Blood Flow Being Higher than Preset Blood Flow?

Background: In recent years, many reports have investigated the usefulness of brachial artery blood flow (BAF) measured by ultrasonography as an evaluation index for the vascular access (VA) stenosis of hemodialysis patients. However, the mechanism of VA dysfunction, despite BAF being higher than the preset blood flow, has not been clarified to date. Methods: The relationship between actual blood-removal flow and recirculation rate with decreasing VA flow was examined using a VA flow path model and pure water as a model fluid. The blood-flow rate was set at 180 mL/min, and the set VA flow rate was lowered stepwise from 350 to 50 mL/min. VA flow rate, blood-removal flow rate, and flow waveform measured between two needle-puncture sites were recorded, and then the actual blood-removal flow rate and recirculation rate were calculated. Results: Recirculation was observed at a VA flow rate < 300 mL/min. The recirculation was due to the VA flow rate, which was transiently reduced to the level below the blood-removal flow rate, resulting in backflow. In contrast, no decrease in the actual blood-removal flow rate was observed. Conclusion: It is suggested that the mechanism of the VA dysfunction, despite the BAF being higher than the preset blood-flow rate, was due to the diastolic BAF being lower than the blood-removal flow rate.

Cellular and Molecular Targets for Non-Invasive, Non-Pharmacological Therapeutic/Rehabilitative Interventions in Acute Ischemic Stroke

BACKGROUND: Cerebral circulation delivers the blood flow to the brain through a dedicated network of sanguine vessels. A healthy human brain can regulate cerebral blood flow (CBF) according to any physiological or pathological challenges. The brain is protected by its self-regulatory mechanisms, which are dependent on neuronal and support cellular populations, including endothelial ones, as well as metabolic, and even myogenic factors. OBJECTIVES: Accumulating data suggest that “non-pharmacological” approaches might provide new opportunities for stroke therapy, such as electro-/acupuncture, hyperbaric oxygen therapy, hypothermia/cooling, photobiomodulation, therapeutic gases, transcranial direct current stimulations, or transcranial magnetic stimulations. We reviewed the recent data on the mechanisms and clinical implications of these non-pharmaceutical treatments. METHODS: To present the state-of-the-art for currently available non-invasive, non-pharmacological-related interventions in acute ischemic stroke, we accomplished this synthetic and systematic literature review based on the Preferred Reporting Items for Systematic Principles Reviews and Meta-Analyses (PRISMA). RESULTS: The initial number of obtained articles was 313. After fulfilling the five steps in the filtering/selection methodology, 54 fully eligible papers were selected for synthetic review. We enhanced our documentation with other bibliographic resources connected to our subject, identified in the literature within a non-standardized search, to fill the knowledge gaps. Fifteen clinical trials were also identified. DISCUSSION: Non-invasive, non-pharmacological therapeutic/rehabilitative interventions for acute ischemic stroke are mainly holistic therapies. Therefore, most of them are not yet routinely used in clinical practice, despite some possible beneficial effects, which have yet to be supplementarily proven in more related studies. Moreover, few of the identified clinical trials are already completed and most do not have final results. CONCLUSIONS: This review synthesizes the current findings on acute ischemic stroke therapeutic/rehabilitative interventions, described as non-invasive and non-pharmacological.

Hemodynamic and Lactate Response to Exhaustive Exercise with L-Arginine Supplementation

Introduction: To further understand the effects of L-arginine on both its ability to enhance lactate clearance and increase overall blood flow before, during, and after exhaustive anaerobic exercise. Methods: Twelve healthy male subjects between the ages of 18-25 first completed an initial visit where baseline data was recorded. Subjects completed three additional visits, in which they ingested either a placebo, two-gram or four-gram dose of L-arginine. Blood flow (BF) and lactate were recorded before ingestion of the treatment, 5 and 15-minutes post-ingestion prior to performing a push-up test to volitional fatigue. Immediately following the push-up test, BF and lactate were assessed and again 15-minutes post exercise. Results: Blood lactate did not differ across condition (p=0.569). Lactate clearance was not influenced by L-arginine when analyzing the Area Under Curve. Blood flow increased with ingestion of the four-gram dose while at rest (the 15-minute mark). Blood flow was also enhanced in the four-gram dose immediately after exercise at the 25-minute mark. Conclusions: The data suggests that a four-gram dose of L-arginine plays a more significant role in blood flow than the clearance of lactate after exercise compared to a two-gram dose or placebo.