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
Department of Neurology, University Hospital Münster, University of Münster, Münster, Germany.
Translational Research Imaging Center, University of Münster, Münster, Germany.
Front Neurol. 2024 Sep 20;15:1341958. doi: 10.3389/fneur.2024.1341958. eCollection 2024.
A dietary supplementation with conjugated linoleic acid (CLA) was shown to attenuate inflammation and increase the proportions of circulating regulatory T cells (T) and M2-type macrophages in disease models such as autoimmune encephalitis and arteriosclerosis. Since T 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.
Functional assessment was performed over 90 days after induction of experimental photothrombotic stroke in wild type mice ( = 37, sham = 10). Subsequently, immunological characterization of different immunological compartments ( = 16), magnetic resonance (MR, = 12) imaging and immunohistochemical staining ( = 8) was performed. Additionally, we tested the effect of CLA on peripheral blood mononuclear cells from human stroke patients and healthy controls ( = 12).
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 treatment with CLA.
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 .
在自身免疫性脑炎和动脉硬化等疾病模型中,膳食补充共轭亚油酸(CLA)可减轻炎症,并增加循环调节性T细胞(T细胞)和M2型巨噬细胞的比例。由于发现T细胞和抗炎(M2型)巨噬细胞可促进中风恢复,我们推测补充CLA可能通过免疫调节作用改善中风恢复。
在野生型小鼠(n = 37,假手术组n = 10)诱导实验性光血栓性中风后90天进行功能评估。随后,对不同免疫区室(n = 16)进行免疫学表征、磁共振(MR,n = 12)成像和免疫组织化学染色(n = 8)。此外,我们测试了CLA对人类中风患者和健康对照者外周血单个核细胞(n = 12)的影响。
磁共振扩散张量成像(DTI)显示,半球间白质束的微观结构重组增强,这取决于病变大小。90天内的功能恢复未受影响。对各个区室进行的详细免疫学分析显示,CLA不会引起显著的长期免疫学改变。然而,对中风后人类血液样本的分析表明,用CLA治疗后,T淋巴细胞释放的促炎干扰素-γ(IFN-γ)和肿瘤坏死因子α(TNF-α)水平降低。
我们旨在探索一种膳食干预措施的疗效,这种干预措施已知副作用最小,中风患者无论残疾程度如何均可采用,且无积极免疫调节疗法相关风险。我们的主要发现包括小梗死灶中微观结构重组改善以及人类T细胞炎症反应降低。