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There is only one known portal system in the mammalian brain - that of the pituitary gland, first identified in 1933 by Popa and Fielding. Here we describe a second portal pathway in the mouse linking the capillary vessels of the brain’s clock suprachiasmatic nucleus (SCN) to those of the organum vasculosum of the lamina terminalis (OVLT), a circumventricular organ. The localized blood vessels of portal pathways enable small amounts of important secretions to reach their specialized targets in high concentrations without dilution in the general circulatory system. These brain clock portal vessels point to an entirely new route and targets for secreted SCN signals, and potentially restructures our understanding of brain communication pathways., The first known portal system in the mammalian brain was identified in 1933. Here the authors describe a new portal system between the capillary beds of the Suprachiasmatic Nucleus master clock and a circumventricular organ, enabling humoral signals to reach targets without dilution in the systemic circulation.

Arteriovenous malformation (AVM) results from errors in vascular development during embryogenesis; absent capillary beds lead to shunting directly from the arterial to venous circulation. Although it is common in the head and neck region, AVMs located in the parotid gland are quite rare. Here, we report two cases of arteriovenous malformation of the parotid gland that presented to our out-patient setup with swelling in the parotid region and were diagnosed as arteriovenous malformation on histopathological study after surgical resection.

Although our current knowledge of the pathophysiology of COVID-19 is still fragmentary, the information so far accrued on the tropism and life cycle of its etiological agent SARS-CoV-2, together with the emerging clinical data, suffice to indicate that the severe acute pulmonary syndrome is the main, but not the only manifestation of COVID-19. Necropsy studies are increasingly revealing underlying endothelial vasculopathies in the form of micro-haemorrhages and micro-thrombi. Intertwined with defective antiviral responses, dysregulated coagulation mechanisms, abnormal hyper-inflammatory reactions and responses, COVID-19 is disclosing a wide pathophysiological palette. An additional property in categorising the disease is the combination of tissue (e.g. neuro- and vasculo-tropism) with organ tropism, whereby the virus preferentially attacks certain organs with highly developed capillary beds, such as the lungs gastrointestinal tract, kidney and brain. These multiple clinical presentations confirm that the acute respiratory syndrome as described initially is increasingly unfolding as a more complex nosological entity, a multiorgan syndrome of systemic breadth. The neurological manifestations of COVID-19, the focus of this review, reflect this manifold nature of the disease. Fil: Barrantes, Francisco Jose. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina

Objective The purpose of this paper was to review the literature regarding the mechanisms leading to degeneration in intervertebral disks and to discuss contributing mechanical and biological factors. Methods The inclusion criteria for the literature review were research studies conducted in the last 3 decades with free full-text available in English. Review articles and articles pertaining to temporomandibular joints and joints of the body other than the intervertebral disk were excluded. The following databases were searched: PubMed, EBSCOhost, and Google Scholar through September 9, 2016. Results A total of 57 articles were used in this review. Intervertebral disk cells require glucose for sustainability and oxygen to synthesize matrix components. Nutrients enter the disk via 2 vascular supply routes: capillary beds of end plates and the peripheral annulus fibrosus. Solute size, shape and charge, compression, and metabolic demand all influence the efficiency of nutrient transport, and alterations of any of these factors may have effects on nutrient transport and, potentially, disk degeneration. Conclusions Progressive nutrient transport disruptions may actively contribute in advancing the phases of degenerative disk disease. Such disruptions include dysfunctional loading and spinal position, lack of motion, high frequency loading, disk injury, aging, smoking, an acidic environment, and a lack of nutrient bioavailability.

Promoting regeneration using scaffolds created by decellularizing native tissue is becoming a popular technique applied to a variety of tissues. We demonstrate a method to decellularize highly vascular tissue keeping the vascular structure intact down to the capillary scale. Using vascular corrosion casting (VCC), we created a method for quantitatively assessing the functionality of vascular extracellular matrix (ECM) following decellularization. Murine lung tissue was decellularized using a number of techniques, then characterized using standard histological methods, as well as our quantitative VCC (qVCC) technique. Using an optimized acellular method, we successfully decellularized lung tissue while leaving behind a patent vascular network based on qualitative and quantitative histological methods.

The mammalian ear has an extraordinary capacity to detect very low-level acoustic signals from the environment. Sound pressures as low as a few μPa (−10 dB SPL) can activate cochlear hair cells. To achieve this sensitivity, biological noise has to be minimized including that generated by cardiovascular pulsation. Generally, cardiac pressure changes are transmitted to most peripheral capillary beds; however, such signals within the stria vascularis of the cochlea would be highly disruptive. Not least, it would result in a constant auditory sensation of heartbeat. We investigate special adaptations in cochlear vasculature that serve to attenuate cardiac pulse signals. We describe the structure of tortuous arterioles that feed stria vascularis as seen in corrosion casts of the cochlea. We provide a mathematical model to explain the role of this unique vascular anatomy in dampening pulsatile blood flow to the stria vascularis.

PET is a powerful technique for measuring the regional metabolism of radiolabelled tracers in vivo, but the question remains how to convert the clearance of an analogue tracer measured by PET to the clearance of its mother substance, e.g., for [18F]fluoro-2-deoxy-D-glucose (18F-FDG) and glucose. The ratio between the extraction fraction of the tracer (E*) and that of the mother substance (E), as measured by arteriovenous concentrations across the organ, is often used as a proportionality factor for converting the PET-determined clearance of tracer to the clearance of the mother substance. However, this approach is founded in compartmental modelling which assumes a well-mixed concentration in the vascular compartment equal to the inlet (arterial) blood concentration. For the in vivo situation with perfused capillaries (for the liver, sinusoids), the removal of substrate from the blood by the cells creates concentration gradients in the capillary/sinusoid. We recently derived and validated that the lumped constant (L) equals ln(1nE*)/ln(1n E), being a correct in vivo proportionality factor in capillary beds for the removal of tracer and mother substance in the cells. This relationship is independent of the concentration of the mother substance, whereas E*/E may vary with the concentration of the mother substance.

Author summary After an ischaemic stroke—one where a clot blocks a major artery in the brain—patients can undergo a procedure where the clot is removed mechanically via a catheter—a thrombectomy. This reopens the blocked vessel, yet some patients don’t achieve blood flow returning to their tissue downstream. One hypothesis for this phenomenon is that the clot fragments into smaller clots (called micro-emboli) which block smaller vessels downstream. However, this can’t be measured in patients due to the inability of clinical imaging resolving the micro-scale. We therefore develop a computational model here, based on experimental thrombectomy data, to quantify the impact of micro-emboli on blood flow in the brain after the removal of a clot. With this model, we found that micro-emboli are a likely contributor to the no-reflow phenomenon after a thrombectomy. Individual blood vessel geometries, clot composition, and thrombectomy technique all impacted the effect of micro-emboli on blood flow and should be taken into consideration to minimise the impact of micro-emboli in the brain. Furthermore, the computational model developed here allows us to now build large-scale models of blood flow in the brain, and hence simulate stroke and the impact of micro-emboli on the entire brain., Many ischaemic stroke patients who have a mechanical removal of their clot (thrombectomy) do not get reperfusion of tissue despite the thrombus being removed. One hypothesis for this ‘no-reperfusion’ phenomenon is micro-emboli fragmenting off the large clot during thrombectomy and occluding smaller blood vessels downstream of the clot location. This is impossible to observe in-vivo and so we here develop an in-silico model based on in-vitro experiments to model the effect of micro-emboli on brain tissue. Through in-vitro experiments we obtain, under a variety of clot consistencies and thrombectomy techniques, micro-emboli distributions post-thrombectomy. Blood flow through the microcirculation is modelled for statistically accurate voxels of brain microvasculature including penetrating arterioles and capillary beds. A novel micro-emboli algorithm, informed by the experimental data, is used to simulate the impact of micro-emboli successively entering the penetrating arterioles and the capillary bed. Scaled-up blood flow parameters–permeability and coupling coefficients–are calculated under various conditions. We find that capillary beds are more susceptible to occlusions than the penetrating arterioles with a 4x greater drop in permeability per volume of vessel occluded. Individual microvascular geometries determine robustness to micro-emboli. Hard clot fragmentation leads to larger micro-emboli and larger drops in blood flow for a given number of micro-emboli. Thrombectomy technique has a large impact on clot fragmentation and hence occlusions in the microvasculature. As such, in-silico modelling of mechanical thrombectomy predicts that clot specific factors, interventional technique, and microvascular geometry strongly influence reperfusion of the brain. Micro-emboli are likely contributory to the phenomenon of no-reperfusion following successful removal of a major clot.