Early loss of pericytes and perivascular stromal cell-induced scar formation after stroke

Despite its limited regenerative capacity, the central nervous system (CNS) shares more repair mechanisms with peripheral tissues than previously recognized. Scar formation is a ubiquitous healing mechanism aimed at patching tissue defects via the generation of fibrous extracellular matrix (ECM). This process, orchestrated by stromal cells, can unfavorably affect the capacity of tissues to restore function. Vascular mural cells have been found to contribute to scarring after spinal cord injury. In the case of stroke, little is known about the responses of pericytes (PCs) and stromal cells. Here, we show that capillary PCs are rapidly lost after cerebral ischemia in both experimental and human stroke. Coincident with this loss is a massive proliferation of resident platelet-derived growth factor receptor beta (PDGFRβ)⁺ and CD105⁺ stromal cells, which originate from the neurovascular unit and deposit ECM in the ischemic mouse brain. The presence of PDGFRβ⁺ stromal cells demarcates a fibrotic, contracted, and macrophage-laden lesion core from the rim of hypertrophic astroglia in both experimental and human stroke. We suggest that a previously unrecognized population of CNS-resident stromal cells drives a dynamic process of scarring after cerebral ischemia, which appears distinct from the glial scar and represents a novel target for regenerative stroke therapies.     

Effect of glutamate receptor antagonists on migrating neural progenitor cells

Neurotransmitters such as glutamate are potential regulators of neurogenesis. Interference with defined glutamate receptor subtypes affects proliferation, migration and differentiation of neural progenitor cells. The cellular targets for the actions of different glutamate receptor ligands are less well known. In this study we have combined calcium imaging, measurement of membrane potential, time‐lapse imaging and immunocytochemistry to obtain a spatial overview of migrating mouse embryonic neural progenitor cell‐derived cells responding to glutamate receptor agonists and antagonists. Responses via metabotropic glutamate receptor 5 correlated with radial glial cells and dominated in the inner migration zones close to the neurosphere. Block of metabotropic glutamate receptor 5 resulted in shorter radial glial processes, a transient increase in neuron‐like cells emerging from the neurosphere and increased motility of neuron‐like cells. α‐Amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA)/kainate receptors are present on the majority of migrating neuronal cells, which with time accumulate at the outer edge of the migration zone. Blocking these receptors leads to an enhanced extension of radial glial processes and a reduced motility of neuron‐like cells. Our results indicate that functional glutamate receptors have profound effects on the motility of neural progenitor cells. The main target for metabotropic glutamate receptor 5 appears to be radial glial cells while AMPA/kainate receptors are mainly expressed in newborn neuronal cells and regulate the migratory progress of these cells. The results suggest that both metabotropic glutamate receptor 5 and AMPA/kainate receptors are of importance for the guidance of migrating embryonic progenitor cells.     

Radixin expression in microglia after cortical stroke lesion

Stroke induces extensive tissue remodeling, resulting in the activation of several cell types in the brain as well as recruitment of blood‐borne leucocytes. Radixin is part of a cytoskeleton linker protein family with the ability to connect transmembrane proteins to the actin cytoskeleton, promoting cell functions involving a dynamic cytoskeleton such as morphological changes, cell division and migration which are common events of different cell types after stroke. In the healthy adult brain radixin is expressed in Olig2⁺ cells throughout the brain and in neural progenitor cells in the subventricular zone. In the current study, we detected a 2.5 fold increase in the number of radixin positive cells in the peri‐infarct cortex two weeks after the induction of cortical stroke by photothrombosis. Similarly, the number of Olig2⁺ cells increased in the peri‐infarct area after stroke; however, the number of radixin⁺/Olig2⁺ cells was unchanged. Neural progenitor cells maintained radixin expression on their route to the infarct. More surprising however, was the expression of radixin in activated microglia in the peri‐infarct cortex. Seventy percent of Iba1⁺ cells expressed radixin after stroke, a population which was not present in the control brain. Furthermore, activation of radixin was predominantly detected in the peri‐infarct region of oligodendrocyte progenitors and microglia. The specific location of radixin⁺ cells in the peri‐infarct region and in microglia suggests a role for radixin in microglial activation after stroke.     

Adolescents with intellectual disability have reduced postural balance and muscle performance in trunk and lower limbs compared to peers without intellectual disability

For adolescent people with ID, falls are more common compared to peers without ID. However, postural balance among this group is not thoroughly investigated. The aim of this study was to compare balance and muscle performance among adolescents aged between 16 and 20 years with a mild to moderate intellectual disability (ID) to age-matched adolescents without ID. A secondary purpose was to investigate the influence of vision, strength, height and Body Mass Index (BMI) on balance. A group of 100 adolescents with ID and a control group of 155 adolescents without ID were investigated with five balance tests and three strength tests: timed up and go test, one leg stance, dynamic one leg stance, modified functional reach test, force platform test, counter movement jump, sit-ups, and Biering-Sørensen trunk extensor endurance test. The results showed that adolescents with an ID in general had significantly lower scores in the balance and muscle performance tests. The group with ID did not have a more visually dominated postural control compared to the group without ID. Height, BMI or muscle performance had no strong correlations with balance performance. It appears as if measures to improve balance and strength are required already at a young age for people with an ID.     

Consumption of highly processed snacks,sugar‐sweetened beverages and child feeding practices in a rural area of Nicaragua

Appropriate feeding behaviours are important for child growth and development. In societies undergoing nutrition transition, new food items are introduced that may be unfavourable for child health. Set in rural Nicaragua, the aim of this study was to describe the infant and young child feeding (IYCF) practices as well as the consumption of highly processed snack foods (HP snacks) and sugar‐sweetened beverages (SSBs). All households with at least one child 0‐ to 35‐month‐old (n = 1371) were visited to collect information on current IYCF practices in the youngest child as well as consumption of SSBs and HP snacks. Breastfeeding was dominant (98%) among 0‐ to 1‐month‐olds and continued to be prevalent (60%) in the second year, while only 34% of the 0‐ to 5‐month‐olds were exclusively breastfed. Complementary feeding practices were deemed acceptable for only 59% of the 6‐ to 11‐month‐old infants, with low dietary diversity reported for 50% and inadequate meal frequency reported for 30%. Consumption of HP snacks and SSBs was frequent and started early; among 6‐ to 8‐month‐olds, 42% and 32% had consumed HP snacks and SSBs, respectively. The difference between the observed IYCF behaviours and World Health Organization recommendations raises concern of increased risk of infections and insufficient intake of micronutrients that may impair linear growth. The concurrent high consumption of SSBs and HP snacks may increase the risk of displacing the recommended feeding behaviours. To promote immediate and long‐term health, growth and development, there is a need to both promote recommended IYCF practices as well as discourage unfavourable feeding behaviours.     

Cervical Spine Clearance in Trauma Patients with an Unreliable Physical Examination

Background

The objective of this study was to describe and compare the timing of cervical spine clearance in trauma patients with an unreliable physical examination.

Methods

We prospectively included adult trauma patients admitted with a cervical collar and an unreliable clinical examination (as defined by the NEXUS criteria) at two level 1 trauma centers: one in the USA (US) and one in Denmark (DK). We excluded patients with cervical spine injuries requiring a collar or surgery as treatment and patients with a collar placed after hospital arrival. The primary outcome was time from emergency department (ED) arrival to collar removal. Secondary outcomes included time to CT of the cervical spine (CTCS). At the US trauma center, an institutional protocol allowing cervical spine clearance exclusively by CTCS was in place. At the Danish trauma center, cervical spine clearance was based on a clinical evaluation by an orthopedic surgeon, usually after CTCS.

Results

A total of 113 patients were included (US: n = 56; DK: n = 57). The median age was 47 years, and 68% were males. The main reasons for an unreliable physical examination were a Glasgow Coma Scale score below 14 (35%), distracting injuries (26%), cervical spine tenderness (13%) and intoxication (13%). The injury severity score at the US trauma center was higher than at the DK trauma center (median: 17 vs. 11, p = 0.03). Both time to CTCS (median: 41 vs. 18 min, p < 0.0001) and time to collar removal (median: 1042 vs. 49 min, p < 0.0001) were significantly greater at the US trauma center.

Conclusions

Time to collar removal was significantly greater in a trauma center utilizing a cervical spine clearance protocol based on CTCS. As patients may develop complications related to the collar, future studies should clarify how early removal can be implemented without increasing the risk of morbidity.

     

Relationships Between Persistent Organic Pollutants and Circulating Immunoglobulin-Y in Black-Legged Kittiwakes and Atlantic Puffins

Have Although persistent organic pollutants (POPs) may affect the immune system, few field studies actually examined this effect. There are indications that POP exert effects on the immune system; however, in the Arctic ecosystem data are scarce. The aim of this study was to examine immune functions in two medium trophic-positioned seabirds, the black-legged kittiwakes (Rissa tridactyla) and Atlantic puffins (Fratercula arctica). Overall POP concentrations were higher in kittiwakes than puffins and males had significantly higher concentrations than females. Mean concentrations of total polychlorinated biphenyls (ΣPCB₉) were 4700 ± 200 and 9600 ± 1400 ng/g lipid weight and 2800 ± 180 and 3900 ± 200 ng/g lipid weight in female and male kittiwake and puffin blood, respectively. Levels of immunoglobulin-Y (IgY) in blood of kittiwakes were not markedly affected by concentrations of POP. Similarly, the primary IgY response to tetanus toxoid was not affected by POP concentrations in a subsample of immunized kittiwakes. In puffins, there were significant correlations between the IgY-response and some of the POPs, but with low explanatory values. These results suggest that POPs concentrations were lower than, or just at the threshold level for effects of the proposed IgY biomarker. It is also conceivable that the IgY levels are not a suitable endpoint for evaluating perturbation of the immune system in free-living seabirds.