RT Journal Article SR Electronic T1 Plasma from healthy donors protects blood–brain barrier integrity via FGF21 and improves the recovery in a mouse model of cerebral ischaemia JF Stroke and Vascular Neurology JO Stroke Vasc Neurol FD BMJ Publishing Group Ltd SP svn-2020-000774 DO 10.1136/svn-2020-000774 A1 Muyassar Mamtilahun A1 Lu Jiang A1 Yaying Song A1 Xiaojing Shi A1 Chang Liu A1 Yixu Jiang A1 Lidong Deng A1 Haoran Zheng A1 Hui Shen A1 Yongfang Li A1 Zhijun Zhang A1 Yongting Wang A1 Yaohui Tang A1 Guo-Yuan Yang YR 2021 UL http://svn.bmj.com/content/early/2021/03/30/svn-2020-000774.abstract AB 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.