AUTHOR=Straeten Frederike A. , Strecker Jan-Kolja , Börsch Anna-Lena , Maus Bastian , Hoppen Maike , Schmeddes Birgit , Härtel Lucia , Fleck Ann-Katrin , van Zyl Stephanie , Straeten Tabea , Beuker Carolin , Koecke Mailin , Mueller-Miny Louisa , Faber Cornelius , Meyer zu Hörste Gerd , Klotz Luisa , Minnerup Jens , Schmidt-Pogoda Antje 

TITLE=A dietary intervention with conjugated linoleic acid enhances microstructural white matter reorganization in experimental stroke

JOURNAL=Frontiers in Neurology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1341958

DOI=10.3389/fneur.2024.1341958

ISSN=1664-2295

ABSTRACT=<sec id="sec1"><title>Background</title><p>A dietary supplementation with conjugated linoleic acid (CLA) was shown to attenuate inflammation and increase the proportions of circulating regulatory T cells (T<sub>regs</sub>) and M2-type macrophages in disease models such as autoimmune encephalitis and arteriosclerosis. Since T<sub>regs</sub> 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.</p></sec><sec id="sec2"><title>Methods</title><p>Functional assessment was performed over 90 days after induction of experimental photothrombotic stroke in wild type mice (<italic>n</italic> = 37, sham <italic>n</italic> = 10). Subsequently, immunological characterization of different immunological compartments (<italic>n</italic> = 16), <italic>ex vivo</italic> magnetic resonance (MR, <italic>n</italic> = 12) imaging and immunohistochemical staining (<italic>n</italic> = 8) was performed. Additionally, we tested the effect of CLA <italic>in vitro</italic> on peripheral blood mononuclear cells from human stroke patients and healthy controls (<italic>n</italic> = 12).</p></sec><sec id="sec3"><title>Results</title><p>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 <italic>in vitro</italic> treatment with CLA.</p></sec><sec sec-type="conclusions" id="sec4"><title>Conclusion</title><p>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 <italic>in vitro</italic>.</p></sec>