CD4(+) CD25(+) forkhead box P3 (FoxP3)(+) regulatory T cells (T reg cells) are known to suppress adaptive immune responses, key control tolerance and autoimmunity.
We challenged the role of CD4(+) T ...reg cells in suppressing established CD8(+) T effector cell responses by using the OT-I/II system in vitro and an OT-I-mediated, oligodendrocyte directed ex vivo model (ODC-OVA model).
CD4(+) T reg cells dampened cytotoxicity of an ongoing CD8(+) T effector cell attack in vitro and within intact central nervous system tissue ex vivo. However, their suppressive effect was limited by the strength of the antigen signal delivered to the CD8(+) T effector cells and the ratio of regulatory to effector T cells. CD8(+) T effector cell suppression required T cell receptor-mediated activation together with costimulation of CD4(+) T reg cells, but following activation, suppression did not require restimulation and was antigen non-specific.
Our results suggest that CD4(+) T reg cells are capable of suppressing CD8(+) T effector cell responses at the parenchymal site, that is, limiting parenchymal damage in autoimmune central nervous system inflammation.
The role of the immune system in the pathophysiology of acute ischemic stroke is increasingly recognized. However, targeted treatment strategies to modulate immunological pathways in stroke are still ...lacking. Glatiramer acetate is a multifaceted immunomodulator approved for the treatment of relapsing-remitting multiple sclerosis. Experimental studies suggest that glatiramer acetate might also work in other neuroinflammatory or neurodegenerative diseases apart from multiple sclerosis.
We evaluated the efficacy of glatiramer acetate in a mouse model of brain ischemia/reperfusion injury. 60 min of transient middle cerebral artery occlusion was induced in male C57Bl/6 mice. Pretreatment with glatiramer acetate (3.5 mg/kg bodyweight) 30 min before the induction of stroke did not reduce lesion volumes or improve functional outcome on day 1.
Glatiramer acetate failed to protect from acute ischemic stroke in our hands. Further studies are needed to assess the true therapeutic potential of glatiramer acetate and related immunomodulators in brain ischemia.
Guided by risk and resilience and attachment perspectives, the present study examined whether teacher–student relationship quality and school climate can buffer against the deleterious effects of ...perceived personal and group ethnic discrimination on psychological and academic domains. We conducted multilevel analyses of seventh graders (40 classrooms; N = 456; 47% female) with different cultural self‐identifications in Germany. Partially confirming pre‐registered hypotheses, results indicated that high levels of perceived personal discrimination were negatively associated with global self‐esteem and emotional school engagement. Contrary to our expectations, neither perceived personal nor group discrimination negatively predicted academic self‐concept. In addition, teacher–student relationship quality but not school climate buffered the relationship between both personal and group discrimination and global self‐esteem and emotional school engagement such that the association was less negative when relationship quality was high. Taken together, our results underscore the importance of considering the different targets of discrimination (i.e., personal self and own group), and that positive teacher–student relationship can be especially beneficial and empowering for youth who are exposed to ethnic discrimination.
With a sample of 2047 German students in 93 classes we investigated whether students' perception of the interestingness of an EFL lesson with intercultural focus was explained by teaching processes, ...students' learning prerequisites, and their interactions. Our findings indicate that lessons during which teachers supported students' self-determination were perceived as more interesting by the students than other lessons. However, even these lessons were not perceived as interesting by all students. Within-class variation was partly explained by students’ personal interest in EFL and intercultural sensitivity. Besides, differential effects of teaching processes were observed depending on these learning prerequisites.
•The study examined students' perception of the interestingness of EFL lessons with an intercultural focus.•Lessons during which teachers supported students' self-determination were perceived as more interesting by students.•Students within each class varied in their perceptions of the interestingness of their respective lesson.•Students' personal interest in EFL and intercultural sensitivity explained part of this variation within classes.•The latter effects were stronger for some lessons than for others depending on teaching processes.
Die Digitalisierung von Studium und Lehre stellt einen komplexen Entwicklungsprozess dar, der für alle beteiligten Akteurinnen und Akteure Herausforderungen, wie beispielsweise die Auseinandersetzung ...mit den Einsatzmöglichkeiten digitaler Medien und die Entwicklung digitaler Kompetenzen, mit sich bringt (Getto und Schulenburg 2018; Kerres 2016). Der Beginn der Corona-Pandemie und die damit verbundene erstmalige Schliessung der Universitäten im Frühjahr 2020 erforderte innerhalb kürzester Zeit die Umstellung der konventionellen universitären Lehre in Präsenzform auf online-gestützte Lehrformate. Wie diese Umstellung von Hochschulangehörigen in Deutschland erlebt wurde, in welchem Ausmass digitale Tools in der eigenen Lehre im Sommersemester 2020 eingesetzt wurden und welche personenbezogenen Merkmale hierfür relevant erscheinen, ist Gegenstand des vorliegenden Beitrags. Die deskriptive Auswertung der bundesweiten Befragung von Dozierenden deutscher Hochschulen verdeutlicht ambivalente Erfahrungen mit der Umstellung auf Online-Lehre. Dennoch wird insgesamt die Bewältigung der pädagogisch-didaktischen Herausforderungen durch die zeitweilige Schliessung der Universitäten aus Sicht der Dozierenden als erfolgreich eingeschätzt. Für das Ausmass der Nutzung digitaler Tools während des Lockdowns zeigen sich in den Korrelationsanalysen signifikante Zusammenhänge mit den bisherigen Vorerfahrungen, der selbsteingeschätzten Fähigkeit, digital zu lehren, sowie Unterschiede zwischen männlichen und weiblichen Befragten.
The digitization of studies and teaching represents a complex development process with challenges for all actors involved, such as dealing with the possible uses of digital media and the development of digital competencies (Getto and Schulenburg 2018; Kerres, 2016). The onset of the Corona pandemic and the associated first-time closure of universities in spring 2020 required the transition from conventional university teaching in face-to-face form to online-supported teaching formats within a very short time. How this transition was experienced by university staff in Germany, to what extent digital tools were used in their own teaching during the summer semester 2020 and which personal characteristics appear to be relevant for this is the subject of this paper. The descriptive analysis of the nationwide survey of teachers at German universities reveals ambivalent experiences with the transition to online teaching. Nevertheless, from the point of view of the university teachers, the overcoming of the pedagogical-didactic challenges caused by the temporary closure of the universities is assessed as successful overall. For the extent of the use of digital tools during the first lockdown, significant correlations with previous experience, self-assessed ability to teach digitally, and differences between male and female respondents emerge in the correlation analyses.
Die Digitalisierung von Studium und Lehre stellt einen komplexen Entwicklungsprozess dar, der für alle beteiligten Akteurinnen und Akteure Herausforderungen, wie beispielsweise die Auseinandersetzung ...mit den Einsatzmöglichkeiten digitaler Medien und die Entwicklung digitaler Kompetenzen, mit sich bringt (Getto und Schulenburg 2018; Kerres 2016). Der Beginn der Corona-Pandemie und die damit verbundene erstmalige Schliessung der Universitäten im Frühjahr 2020 erforderte innerhalb kürzester Zeit die Umstellung der konventionellen universitären Lehre in Präsenzform auf online-gestützte Lehrformate. Wie diese Umstellung von Hochschulangehörigen in Deutschland erlebt wurde, in welchem Ausmass digitale Tools in der eigenen Lehre im Sommersemester 2020 eingesetzt wurden und welche personenbezogenen Merkmale hierfür relevant erscheinen, ist Gegenstand des vorliegenden Beitrags. Die deskriptive Auswertung der bundesweiten Befragung von Dozierenden deutscher Hochschulen verdeutlicht ambivalente Erfahrungen mit der Umstellung auf Online-Lehre. Dennoch wird insgesamt die Bewältigung der pädagogisch-didaktischen Herausforderungen durch die zeitweilige Schliessung der Universitäten aus Sicht der Dozierenden als erfolgreich eingeschätzt. Für das Ausmass der Nutzung digitaler Tools während des Lockdowns zeigen sich in den Korrelationsanalysen signifikante Zusammenhänge mit den bisherigen Vorerfahrungen, der selbsteingeschätzten Fähigkeit, digital zu lehren, sowie Unterschiede zwischen männlichen und weiblichen Befragten.
Objective
Recent evidence suggests that ischemic stroke is a thromboinflammatory disease. Plasma kallikrein (PK) cleaves high–molecular‐weight kininogen to release bradykinin (BK) and is a key ...constituent of the proinflammatory contact‐kinin system. In addition, PK can activate coagulation factor XII, the origin of the intrinsic coagulation cascade. Thus, PK triggers 2 important pathological pathways of stroke formation, thrombosis and inflammation.
Methods
We investigated the consequences of PK inhibition in transient and permanent models of ischemic stroke.
Results
PK‐deficient mice of either sex challenged with transient middle cerebral artery occlusion developed significantly smaller brain infarctions and less severe neurological deficits compared with controls without an increase in infarct‐associated hemorrhage. This protective effect was preserved at later stages of infarctions as well as after permanent stroke. Reduced intracerebral thrombosis and improved cerebral blood flow could be identified as underlying mechanisms. Moreover, blood–brain barrier function was maintained in mice lacking PK, and the local inflammatory response was reduced. PK‐deficient mice reconstituted with PK or BK again developed brain infarctions similar to wild‐type mice. Important from a translational perspective, inhibition of PK in wild‐type mice using a PK‐specific antibody was likewise effective even when performed in a therapeutic setting up to 3 hours poststroke.
Interpretation
PK drives thrombus formation and inflammation via activation of the intrinsic coagulation cascade and the release of BK but appears to be dispensable for hemostasis. Hence, PK inhibition may offer a safe strategy to combat thromboembolic disorders including ischemic stroke. Ann Neurol 2015;77:784–803
The blood-brain barrier (BBB) is an integral part of the neurovascular unit (NVU). The NVU is comprised of endothelial cells that are interconnected by tight junctions resting on a parenchymal ...basement membrane ensheathed by pericytes, smooth muscle cells and a layer of astrocyte end feet. Circulating blood cells, such as leukocytes, complete the NVU. BBB disruption is common in several neurological diseases, but the molecular mechanisms involved remain largely unknown. We analyzed the role of TWIK-related potassium channel-1 (TREK1, encoded by KCNK2) in human and mouse endothelial cells and the BBB. TREK1 was downregulated in endothelial cells by treatment with interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). Blocking TREK1 increased leukocyte transmigration, whereas TREK1 activation had the opposite effect. We identified altered mitogen-activated protein (MAP) kinase signaling, actin remodeling and upregulation of cellular adhesion molecules as potential mechanisms of increased migration in TREK1-deficient (Kcnk2(-/-)) cells. In Kcnk2(-/-) mice, brain endothelial cells showed an upregulation of the cellular adhesion molecules ICAM1, VCAM1 and PECAM1 and facilitated leukocyte trafficking into the CNS. Following the induction of experimental autoimmune encephalomyelitis (EAE) by immunization with a myelin oligodendrocyte protein (MOG)35-55 peptide, Kcnk2(-/-) mice showed higher EAE severity scores that were accompanied by increased cellular infiltrates in the central nervous system (CNS). The severity of EAE was attenuated in mice given the amyotrophic lateral sclerosis drug riluzole or fed a diet enriched with linseed oil (which contains the TREK-1 activating omega-3 fatty acid α-linolenic acid). These beneficial effects were reduced in Kcnk2(-/-) mice, suggesting TREK-1 activating compounds may be used therapeutically to treat diseases related to BBB dysfunction.
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