RESUMEN
Although the roles of embryonic yolk sac-derived, resident microglia in neurodevelopment were extensively studied, the possible involvement of bone marrow-derived cells remains elusive. In this work, we used a fate-mapping strategy to selectively label bone marrow-derived cells and their progeny in the brain (FLT3+IBA1+). FLT3+IBA1+ cells were confirmed to be transiently present in the healthy brain during early postnatal development. FLT3+IBA1+ cells have a distinct morphology index at postnatal day(P)0, P7, and P14 compared with neighboring microglia. FLT3+IBA1+ cells also express the microglial markers P2RY12 and TMEM119 and interact with VGLUT1 synapses at P14. Scanning electron microscopy indeed showed that FLT3+ cells contact and engulf pre-synaptic elements. Our findings suggest FLT3+IBA1+ cells might assist microglia in their physiological functions in the developing brain including synaptic pruning which is performed using their purinergic sensors. Our findings stimulate further investigation on the involvement of peripheral macrophages during homeostatic and pathological development.
RESUMEN
Background: Low back pain (LBP) accounts for a significant proportion of primary care visits. Despite the development of evidence-based guidelines, studies point to the inefficient use of healthcare resources, resulting in over 60.0% of patients with LBP being referred to spine surgeons without any surgical indication. Centralized waiting lists (CWLs) have been implemented to improve access to specialized care by managing asymmetry between supply and demands. To date, no study has provided data on patients' clinical profiles and referral patterns to medical specialists for LBP in the context of a publicly funded healthcare system operating a prioritization model. The objective of this study was to evaluate the appropriateness of specialized care referrals for LBP after the implementation of a CWL. Methods: A retrospective cross-sectional analysis of 500 randomly selected electronic health records of patients who attended the outpatient neurosurgery clinic of the administrative Mauricie-et-Centre-du-Québec region was performed. Inclusion criteria were neurosurgery consultation referrals for adults ≥18 years suffering from a primary complaint of LBP, and performed between September 1st, 2018, and September 1st, 2021. Data relevant for drawing a comprehensive portrait of patients referred to the neurosurgery service and for judging referrals appropriateness were manually extracted. Results: Of the 500 cases analyzed, only 112 (22.4%) were surgical candidates, while 221 (44.2%) were discharge from the neurosurgery service upon initial assessment. Key information was inconsistently documented in medical files, thus preventing the establishment of a comprehensive portrait of patients referred to the neurosurgery service for LBP. Nevertheless, over 80.0% of referrals made during the study period were deemed inappropriate. Inappropriate referrals were characterized by higher proportion of patients symptomatically improved, presenting a back-dominant chief complaint, exhibiting no objective neurological symptoms, and diagnosed with non-specific LBP. Conclusion: This study reveals a significant proportion of inappropriate referrals to specialized care for LBP. Further research is needed to better understand the factors that prompt referrals to medical specialists for LBP, and the criteria considered by neurosurgeons when selecting the appropriate management strategy. Recent studies suggest that triaging approaches led by musculoskeletal experts may improve referral appropriateness to specialized care.
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Coronavirus disease 2019 (COVID-19) is marked by cardio-respiratory alterations, with increasing reports also indicating neurological and psychiatric symptoms in infected individuals. During COVID-19 pathology, the central nervous system (CNS) is possibly affected by direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invasion, exaggerated systemic inflammatory responses, or hypoxia. Psychosocial stress imposed by the pandemic further affects the CNS of COVID-19 patients, but also the non-infected population, potentially contributing to the emergence or exacerbation of various neurological or mental health disorders. Microglia are central players of the CNS homeostasis maintenance and inflammatory response that exert their crucial functions in coordination with other CNS cells. During homeostatic challenges to the brain parenchyma, microglia modify their density, morphology, and molecular signature, resulting in the adjustment of their functions. In this review, we discuss how microglia may be involved in the neuroprotective and neurotoxic responses against CNS insults deriving from COVID-19. We examine how these responses may explain, at least partially, the neurological and psychiatric manifestations reported in COVID-19 patients and the general population. Furthermore, we consider how microglia might contribute to increased CNS vulnerability in certain groups, such as aged individuals and people with pre-existing conditions.
RESUMEN
The immune system is essential for maintaining homeostasis, as well as promoting growth and healing throughout the brain and body. Considering that immune cells respond rapidly to changes in their microenvironment, they are very difficult to study without affecting their structure and function. The advancement of non-invasive imaging methods greatly contributed to elucidating the physiological roles performed by immune cells in the brain across stages of the lifespan and contexts of health and disease. For instance, techniques like two-photon in vivo microscopy were pivotal for studying microglial functional dynamics in the healthy brain. Through these observations, their interactions with neurons, astrocytes, blood vessels and synapses were uncovered. High-resolution electron microscopy with immunostaining and 3D-reconstruction, as well as super-resolution fluorescence microscopy, provided complementary insights by revealing microglial interventions at synapses (phagocytosis, trogocytosis, synaptic stripping, etc.). In addition, serial block-face scanning electron microscopy has provided the first 3D reconstruction of a microglial cell at nanoscale resolution. This review will discuss the technical toolbox that currently allows to study microglia and other immune cells in the brain, as well as introduce emerging methods that were developed and could be used to increase the spatial and temporal resolution of neuroimmune imaging. A special attention will also be placed on positron emission tomography and the development of selective functional radiotracers for microglia and peripheral macrophages, considering their strong potential for research translation between animals and humans, notably when paired with other imaging modalities such as magnetic resonance imaging.