Background Healthy plasma therapy reverses cognitive deficits and promotes neuroplasticity in ageing brain disease. However, whether healthy plasma therapy improve blood–brain barrier integrity after stroke remains unknown. Methods Here, we intravenously injected healthy female mouse plasma into adult female ischaemic stroke C57BL/6 mouse induced by 90 min transient middle cerebral artery occlusion for eight consecutive days. Infarct volume, brain atrophy and neurobehavioural tests were examined to assess the outcomes of plasma treatment. Cell apoptosis, blood–brain barrier integrity and fibroblast growth factor 21 knockout mice were used to explore the underlying mechanism. Results Plasma injection improved neurobehavioural recovery and decreased infarct volume, brain oedema and atrophy after stroke. Immunostaining showed that the number of transferase dUTP nick end labelling+/NeuN+ cells decreased in the plasma-injected group. Meanwhile, plasma injection reduced ZO-1, occluding and claudin-5 tight junction gap formation and IgG extravasation at 3 days after ischaemic stroke. Western blot results showed that the FGF21 expression increased in the plasma-injected mice. However, using FGF21 knockout mouse plasma injecting to the ischaemic wild-type mice diminished the neuroprotective effects. Conclusions Our study demonstrated that healthy adult plasma treatment protected the structural and functional integrity of blood–brain barrier, reduced neuronal apoptosis and improved functional recovery via FGF21, opening a new avenue for ischaemic stroke therapy. All data relevant to the study are included in the article or uploaded as online supplemental information. The data that support the findings of this study are available from the corresponding author on reasonable request.

中文翻译：

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来自健康供体的血浆通过 FGF21 保护血脑屏障完整性，并改善脑缺血小鼠模型的恢复

背景健康的血浆疗法可逆转认知缺陷并促进老化脑部疾病的神经可塑性。然而，健康的血浆疗法是否能改善中风后血脑屏障的完整性仍然未知。方法 在这里，我们将健康雌性小鼠血浆静脉注射到成年雌性缺血性卒中 C57BL/6 小鼠体内，该小鼠通过 90 分钟的短暂大脑中动脉闭塞连续 8 天诱导。检查梗塞体积、脑萎缩和神经行为测试以评估血浆治疗的结果。细胞凋亡、血脑屏障完整性和成纤维细胞生长因子 21 敲除小鼠用于探索潜在机制。结果 血浆注射改善了神经行为恢复，减少了中风后的梗塞体积、脑水肿和萎缩。免疫染色显示血浆注射组中转移酶 dUTP 缺口末端标记+/NeuN+ 细胞的数量减少。同时，在缺血性卒中后3天，血浆注射减少了ZO-1、闭塞和claudin-5紧密连接间隙的形成和IgG外渗。Western印迹结果显示，注射血浆的小鼠中FGF21表达增加。然而，将 FGF21 敲除小鼠血浆注射到缺血性野生型小鼠中会降低神经保护作用。结论 我们的研究表明，健康成人血浆治疗通过 FGF21 保护了血脑屏障的结构和功能完整性，减少了神经元凋亡并改善了功能恢复，为缺血性中风治疗开辟了一条新途径。所有与研究相关的数据都包含在文章中或作为在线补充信息上传。支持本研究结果的数据可根据合理要求从相应作者处获得。