Antigen-specific immune reactions to ischemic stroke

Brain proteins are detected in the cerebrospinal fluid (CSF) and blood of stroke patients and their concentration is related to the extent of brain damage. Antibodies against brain antigens develop after stroke, suggesting a humoral immune response to the brain injury. Furthermore, induced immune tolerance is beneficial in animal models of cerebral ischemia. The presence of circulating T cells sensitized against brain antigens, and antigen presenting cells (APCs) carrying brain antigens in draining lymphoid tissue of stroke patients support the notion that stroke might induce antigen-specific immune responses. After stroke, brain proteins that are normally hidden from the periphery, inflammatory mediators, and danger signals can exit the brain through several efflux routes. They can reach the blood after leaking out of the damaged blood-brain barrier (BBB) or following the drainage of interstitial fluid to the dural venous sinus, or reach the cervical lymph nodes through the nasal lymphatics following CSF drainage along the arachnoid sheaths of nerves across the nasal submucosa. The route and mode of access of brain antigens to lymphoid tissue could influence the type of response. Central and peripheral tolerance prevents autoimmunity, but the actual mechanisms of tolerance to brain antigens released into the periphery in the presence of inflammation, danger signals, and APCs, are not fully characterized. Stroke does not systematically trigger autoimmunity, but under certain circumstances, such as pronounced systemic inflammation or infection, autoreactive T cells could escape the tolerance controls. Further investigation is needed to elucidate whether antigen-specific immune events could underlie neurological complications impairing recovery from stroke

Antigen-specific immune reactions to ischemic stroke

Brain proteins are detected in the cerebrospinal fluid (CSF) and blood of stroke patients and their concentration is related to the extent of brain damage. Antibodies against brain antigens develop after stroke, suggesting a humoral immune response to the brain injury. Furthermore, induced immune tolerance is beneficial in animal models of cerebral ischemia. The presence of circulating T cells sensitized against brain antigens, and antigen presenting cells (APCs) carrying brain antigens in draining lymphoid tissue of stroke patients support the notion that stroke might induce antigen-specific immune responses. After stroke, brain proteins that are normally hidden from the periphery, inflammatory mediators, and danger signals can exit the brain through several efflux routes. They can reach the blood after leaking out of the damaged blood-brain barrier (BBB) or following the drainage of interstitial fluid to the dural venous sinus, or reach the cervical lymph nodes through the nasal lymphatics following CSF drainage along the arachnoid sheaths of nerves across the nasal submucosa. The route and mode of access of brain antigens to lymphoid tissue could influence the type of response. Central and peripheral tolerance prevents autoimmunity, but the actual mechanisms of tolerance to brain antigens released into the periphery in the presence of inflammation, danger signals, and APCs, are not fully characterized. Stroke does not systematically trigger autoimmunity, but under certain circumstances, such as pronounced systemic inflammation or infection, autoreactive T cells could escape the tolerance controls. Further investigation is needed to elucidate whether antigen-specific immune events could underlie neurological complications impairing recovery from stroke

Niveles de estrés-recuperación en esquiadoras de alto rendimiento

El balance entre los niveles de estrés y de recuperación en los deportistas es necesario para alcanzar un estado óptimo de rendimiento y competir con garantías en el alto rendimiento deportivo. El objetivo de este estudio es determinar los niveles de estrés-recuperación en deportistas de esquí alpino de alto rendimiento en función del nivel de carga externa en tres momentos de la temporada. Han participado 7 esquiadoras de la Federación Andorrana de Esquí, con una media de edad de 19,43 (SD=4,08) años. Se administró la versión española del Cuestionario de Estrés-Recuperación para deportistas (RESTQ-76), en tres situaciones de carga diferenciadas (baja, media y alta). Los resultados indicaron valores significativamente superiores en Éxito en la situación de carga media respecto a la situación de carga alta, en Calidad de sueño, en la situación de carga media respecto a las otras dos situaciones y en Autorregulación en la situación de carga alta respecto a la situación de carga baja. El presente estudio evidenció un estado de estrés-recuperación general favorable, y, asimismo, mostró la importancia de la identificación del estado de estrés-recuperación para prevenir el sobreentrenamiento y las lesiones en el esquí alpino.The balance between the levels of stress and recovery in athletes is necessary to achieve an optimal state of performance and compete with guarantees in high-performance sports. The objective of this study is to determine the stress-recovery levels in high-performance alpine ski athletes based on the level of internal load at three times of the season. Seven athletes from the Andorran Ski Federation have participated, with an average age of 19.43 (SD = 4.08) years. The Spanish version of the Stress-Recovery Questionnaire for athletes (RESTQ-76) was administered in three situations differentiated by training load (low, medium, and high). The results indicate significantly higher values ​​in Success in the medium load situation compared to the high load situation, in Sleep quality, in the medium load situation compared to the other two situations and in Self-regulation in the high load situation compared to the low load situation. The present study evidenced a favorable general stress-recovery state and showed the importance of identifying the stress-recovery state to prevent overtraining and injuries in alpine skiing.O equilíbrio entre os níveis de estresse e recuperação nos atletas é necessário para atingir um estado ótimo de desempenho e competir com garantias no alto desempenho esportivo. O objetivo deste estudo é determinar os níveis de recuperação do estresse em esquiadores alpinos de alto rendimento em função do nível de carga externa em três épocas da temporada. Participaram 7 esquiadores da Federação de Esqui de Andorra, com uma idade média de 19,43 (DP = 4,08) anos. A versão em espanhol do Questionário de Recuperação de Stress para atletas (RESTQ-76) foi administrada em três diferentes situações de carga (baixa, média e alta). Os resultados indicaram valores significativamente maiores em Sucesso na situação de carga média em relação à situação de carga alta, em Qualidade do sono, na situação de carga média em relação às outras duas situações e em Autorregulação na situação de carga alta em relação ao situação de carga baixa. O presente estudo mostrou um estado geral de recuperação do estresse favorável, e também mostrou a importância de identificar o estado de recuperação do estresse para prevenir overtraining e lesões no esqui alpino

Cell therapy with hiPSC-derived RPE cells and RPCs prevents visual function loss in a rat model of retinal degeneration

Photoreceptor loss is the principal cause of blindness in retinal degenerative diseases (RDDs). Whereas some therapies exist for early stages of RDDs, no effective treatment is currently available for later stages, and once photoreceptors are lost, the only option to rescue vision is cell transplantation. With the use of the Royal College of Surgeons (RCS) rat model of retinal degeneration, we sought to determine whether combined transplantation of human-induced pluripotent stem cell (hiPSC)-derived retinal precursor cells (RPCs) and retinal pigment epithelial (RPE) cells was superior to RPE or RPC transplantation alone in preserving retinal from degeneration. hiPSC-derived RPCs and RPE cells expressing (GFP) were transplanted into the subretinal space of rats. In vivo monitoring showed that grafted cells survived 12 weeks in the subretinal space, and rats treated with RPE + RPC therapy exhibited better conservation of the outer nuclear layer (ONL) and visual response than RPE-treated or RPC-treated rats. Transplanted RPE cells integrated in the host RPE layer, whereas RPC mostly remained in the subretinal space, although a limited number of cells integrated in the ONL. In conclusion, the combined transplantation of hiPSC-derived RPE and RPCs is a potentially superior therapeutic approach to protect retina from degeneration in RDDs

Fate predetermination of cardiac myocytes during zebrafish heart regeneration

Adult zebrafish have the remarkable ability to regenerate their heart upon injury, a process that involves limited dedifferentiation and proliferation of spared cardiomyocytes (CMs), and migration of their progeny. During regeneration, proliferating CMs are detected throughout the myocardium, including areas distant to the injury site, but whether all of them are able to contribute to the regenerated tissue remains unknown. Here, we developed a CM-specific, photoinducible genetic labelling system, and show that CMs labelled in embryonic hearts survive and contribute to all three (primordial, trabecular and cortical) layers of the adult zebrafish heart. Next, using this system to investigate the fate of CMs from different parts of the myocardium during regeneration, we show that only CMs immediately adjacent to the injury site contributed to the regenerated tissue. Finally, our results show an extensive predetermination of CM fate during adult heart regeneration, with cells from each myocardial layer giving rise to cells that retain their layer identity in the regenerated myocardium. Overall, our results indicate that adult heart regeneration in the zebrafish is a rather static process governed by short-range signals, in contrast to the highly dynamic plasticity of CM fates that takes place during embryonic heart regeneration

Ready for Failure? Irrational Beliefs, Perfectionism and Mental Health in Male Soccer Academy Players

Altres ajuts: acords transformatius de la UABSince Junior-to-Senior Transition (JST) is only considered successful when soccer players become professionals, many junior athletes must cope with failure, and their sporting careers and mental health may be at risk. Therefore, the objectives of this study are to (a) identify different career expectancies of male soccer academy players, and (b) describe irrational beliefs, perfectionism and mental health levels associated with different career expectancies, identifying risk factors in the JST. A total of 515 male soccer players between 14 and 19 years old (M = 16.7; SD = 1.6) who played in Spanish professional youth academies during the 2020-2021 season, answered questionnaires on sports career model, beliefs, perfectionism and mental health (i.e., iPBI, MPS-2 and GHQ-12). The results suggest that the number of juniors who aspire to be professionals (57%) far exceeds the number of players who become professionals (10%; Dugdale in Scandinavian Journal of Medicine & Science in Sports 31:73-84, 2021). Also, results show that this population presents high levels of demandingness (M = 5.5), low frustration tolerance (M = 5.2), self-organization (M = 5.2) and social functioning (M = 5.5), and low scores on depreciation (M = 2.6) and loss of confidence and self-esteem (M = 2.4). In a more detailed way, the results are compared according to expectancies. These academies are usually environments where success and failure are antagonistic concepts, and where perfectionism and irrational beliefs are normalized and integrated among all members of this context. However, the possible maladaptive effects put their mental health at risk. With the aim of rationalizing the concepts of success and failure and protecting their mental health, especially those who will not become professionals, this study proposes a new route based on the REBT philosophy and ARRC technique

Proteomics Analysis of Extracellular Matrix Remodeling During Zebrafish Heart Regeneration

Adult zebrafish, in contrast to mammals, are able to regenerate their hearts in response to injury or experimental amputation. Our understanding of the cellular and molecular bases that underlie this process, although fragmentary, has increased significantly over the last years. However, the role of the extracellular matrix (ECM) during zebrafish heart regeneration has been comparatively rarely explored. Here, we set out to characterize the ECM protein composition in adult zebrafish hearts, and whether it changed during the regenerative response. For this purpose, we first established a decellularization protocol of adult zebrafish ventricles that significantly enriched the yield of ECM proteins. We then performed proteomic analyses of decellularized control hearts and at different times of regeneration. Our results show a dynamic change in ECM protein composition, most evident at the earliest (7 days postamputation) time point analyzed. Regeneration associated with sharp increases in specific ECM proteins, and with an overall decrease in collagens and cytoskeletal proteins. We finally tested by atomic force microscopy that the changes in ECM composition translated to decreased ECM stiffness. Our cumulative results identify changes in the protein composition and mechanical properties of the zebrafish heart ECM during regeneration

Schistosomiasis Among Female Migrants in Non-endemic Countries : Neglected Among the Neglected? A Pilot Study

Schistosomiasis among migrant populations in Europe is an underdiagnosed infection, yet delayed treatment may have serious long-term consequences. In this study we aimed to characterize the clinical manifestations of Schistosoma infection among migrant women, and the degree of underdiagnosis. We carried out a prospective cross-sectional study among a migrant population living in the North Metropolitan Barcelona area and coming from schistosomiasis-endemic countries. We obtained clinical, laboratory and socio-demographic data from electronic clinical records, as well as information about years of residence and previous attendance at health services. Blood sample was obtained and schistosomiasis exposure was assessed using a specific ELISA serological test. Four hundred and five patients from schistosomiasis-endemic regions were screened, of whom 51 (12.6%) were female. Seropositivity prevalence was 54.8%, but considering women alone we found a prevalence of 58.8% (30 out of 51). The median age of the 51 women was 41.0 years [IQR (35-48)] and the median period of residence in the European Union was 13 years [IQR (10-16)]. Schistosoma -positive women (N = 30) showed a higher prevalence of gynecological signs and symptoms compared to the seronegative women (96.4 vs. 66.6%, p = 0.005). Among seropositive women, the median number of visits to Sexual and Reproductive Health unit prior to diagnosis of schistosomiasis was 41 [IQR (18-65)]. The high prevalence of signs and symptoms among seropositive women and number of previous visits suggest a high rate of underdiagnosis and/or delayed diagnosis of Schistosoma infection, particularly female genital schistosomiasis, among migrant females

T Cells Prevent Hemorrhagic Transformation in Ischemic Stroke by P-Selectin Binding

Objective Hemorrhagic transformation is a serious complication of ischemic stroke after recanalization therapies. This study aims to identify mechanisms underlying hemorrhagic transformation after cerebral ischemia/reperfusion. Approach and Results We used wild-type mice and Selplg(-/-) and Fut7(-/-) mice defective in P-selectin binding and lymphopenic Rag2(-/-) mice. We induced 30-minute or 45-minute ischemia by intraluminal occlusion of the middle cerebral artery and assessed hemorrhagic transformation at 48 hours with a hemorrhage grading score, histological means, brain hemoglobin content, or magnetic resonance imaging. We depleted platelets and adoptively transferred T cells of the different genotypes to lymphopenic mice. Interactions of T cells with platelets in blood were studied by flow cytometry and image stream technology. We show that platelet depletion increased the bleeding risk only after large infarcts. Lymphopenia predisposed to hemorrhagic transformation after severe stroke, and adoptive transfer of T cells prevented hemorrhagic transformation in lymphopenic mice. CD4(+) memory T cells were the subset of T cells binding P-selectin and platelets through functional P-selectin glycoprotein ligand-1. Mice defective in P-selectin binding had a higher hemorrhagic score than wild-type mice. Adoptive transfer of T cells defective in P-selectin binding into lymphopenic mice did not prevent hemorrhagic transformation. Conclusions The study identifies lymphopenia as a previously unrecognized risk factor for secondary hemorrhagic transformation in mice after severe ischemic stroke. T cells prevent hemorrhagic transformation by their capacity to bind platelets through P-selectin. The results highlight the role of T cells in bridging immunity and hemostasis in ischemic stroke

CNS-border associated macrophages respond to acute ischemic stroke attracting granulocytes and promoting vascular leakage

The central nervous system (CNS) contains several types of immune cells located in specific anatomic compartments. Macrophages reside at the CNS borders surrounding the brain vessels, in leptomeningeal spaces and the choroid plexus, where they interact with the vasculature and play immunological surveillance and scavenging functions. We investigated the phenotypic changes and role of these macrophages in response to acute ischemic stroke. Given that CD163 expression is a hallmark of perivascular and meningeal macrophages in the rat and human brain, we isolated CD163+ brain macrophages by fluorescence activated cell sorting. We obtained CD163+ cells from control rats and 16 h following transient middle cerebral artery occlusion, after verifying that infiltration of CD163+ peripheral myeloid cells is negligible at this acute time point. Transcriptome analysis of the sorted CD163+ cells identified ischemia-induced upregulation of the hypoxia inducible factor-1 pathway and induction of genes encoding for extracellular matrix components and leukocyte chemoattractants, amongst others. Using a cell depletion strategy, we found that CNS border-associated macrophages participate in granulocyte recruitment, promote the expression of vascular endothelial growth factor (VEGF), increase the permeability of pial and cortical blood vessels, and contribute to neurological dysfunction in the acute phase of ischemia/reperfusion. We detected VEGF expression surrounding blood vessels and in some CD163+ perivascular macrophages in the brain tissue of ischemic stroke patients deceased one day after stroke onset. These findings show ischemia-induced reprogramming of the gene expression profile of CD163+ macrophages that has a rapid impact on leukocyte chemotaxis and blood-brain barrier integrity, and promotes neurological impairment in the acute phase of stroke