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Background: A dietary supplementation with conjugated linoleic acid (CLA) was shown to attenuate inflammation and increase the proportions of circulating regulatory T cells (Tregs) and M2-type macrophages in disease models such as autoimmune encephalitis and arteriosclerosis. Since Tregs and anti-inflammatory (M2-type) macrophages were found to enhance stroke recovery, we hypothesized that CLA-supplementation might improve stroke recovery via immune modulatory effects. Methods: Functional assessment was performed over 90 days after induction of experimental photothrombotic stroke in wild type mice (n = 37, sham n = 10). Subsequently, immunological characterization of different immunological compartments (n = 16), ex vivo magnetic resonance (MR, n = 12) imaging and immunohistochemical staining (n = 8) was performed. Additionally, we tested the effect of CLA in vitro on peripheral blood mononuclear cells from human stroke patients and healthy controls (n = 12). Results: MR diffusion tensor imaging (DTI) demonstrated enhanced microstructural reorganization of interhemispheric white matter tracts, dependent on lesion size. Functional recovery over 90 days remained unaffected. Detailed immunological analyses across various compartments revealed no significant long-term immunological alterations due to CLA. However, analyses of human blood samples post-stroke showed reduced levels of pro-inflammatory interferon-γ (IFN-γ) and tumor necrosis factor alpha (TNF-α) release by T-lymphocytes following in vitro treatment with CLA. Conclusion: We aimed to explore the efficacy of a dietary intervention with minimal known side effects that could be accessible to human stroke patients, regardless of the degree of disability, and without the risks associated with aggressive immunomodulatory therapies. Our main findings include improved microstructural reorganization in small infarcts and a reduced inflammatory response of human T cells in vitro. [ABSTRACT FROM AUTHOR]

Demyelination of corticospinal tract neurons contributes to long‐term disability after cortical stroke. Nonetheless, poststroke myelin loss has not been addressed as a therapeutic target, so far. We hypothesized that an antibody‐mediated inhibition of the Nogo receptor‐interacting protein (LINGO‐1, leucine‐rich repeat and immunoglobulin domain‐containing Nogo receptor‐interacting protein) may counteract myelin loss, enhance remyelination and axonal growth, and thus promote functional recovery following stroke. To verify this hypothesis, mice were subjected to photothrombotic stroke and received either an antibody against LINGO‐1 (n = 19) or a control treatment (n = 18). Behavioral tests were performed to assess the effects of anti‐LINGO‐1 treatment on the functional recovery. Seven weeks after stroke, immunohistochemical analyses were performed to analyze the effect of anti‐LINGO‐1 treatment on myelination and axonal loss of corticospinal tract neurons, proliferation of oligodendrocytes and neurogenesis. Anti‐LINGO‐1 treatment resulted in significantly improved functional recovery (p < 0.0001, repeated measures analysis of variance), and increased neurogenesis in the hippocampus and subventricular zone of the ipsilateral hemisphere (p = 0.0094 and p = 0.032, t‐test). Notably, we observed a significant increase in myelin (p = 0.0295, t‐test), platelet‐derived growth factor receptor α‐positive oligodendrocyte precursor cells (p = 0.0356, t‐test) and myelinating adenomatous polyposis coli‐positive cells within the ipsilateral internal capsule of anti‐LINGO‐1‐treated mice (p = 0.0021, t‐test). In conclusion, we identified anti‐LINGO‐1 as the first neuroregenerative treatment that counteracts poststroke demyelination of corticospinal tract neurons, presumably by increased proliferation of myelin precursor cells, and thereby improves functional recovery. Most importantly, our study presents myelin loss as a novel therapeutic target following stroke. [ABSTRACT FROM AUTHOR]

Inflammatory causes of stroke are frequent and often pose diagnostic and therapeutic challenges due to the scarcity of randomized trials and the absence of clear guideline recommendations for many scenarios. Following the publication of the recommendations of the European Stroke Organization on primary angiitis of the central nervous system (PACNS) last year, the German Neurological Society (DGN) has issued very clear guidelines this year on the diagnostics and treatment of PACNS and updated the recommendations for systemic vasculitides; however, stroke often occurs not only as a result of primary vascular inflammation but also as a complication of another organ infection. Approximately 5% of all patients with sepsis, ca. 20% of patients with bacterial meningitis and up to 40% of patients with bacterial endocarditis suffer from a stroke as a complication. This article summarizes the key characteristics of these inflammatory causes of stroke and particularly focuses on the current recommendations for diagnostic and therapeutic management., (© 2024. The Author(s).)