PT  - JOURNAL ARTICLE
AU  - Mamtilahun, Muyassar
AU  - Jiang, Lu
AU  - Song, Yaying
AU  - Shi, Xiaojing
AU  - Liu, Chang
AU  - Jiang, Yixu
AU  - Deng, Lidong
AU  - Zheng, Haoran
AU  - Shen, Hui
AU  - Li, Yongfang
AU  - Zhang, Zhijun
AU  - Wang, Yongting
AU  - Tang, Yaohui
AU  - Yang, Guo-Yuan
TI  - Plasma from healthy donors protects blood–brain barrier integrity via FGF21 and improves the recovery in a mouse model of cerebral ischaemia
AID  - 10.1136/svn-2020-000774
DP  - 2021 Dec 01
TA  - Stroke and Vascular Neurology
PG  - 561--571
VI  - 6
IP  - 4
4099  - http://svn.bmj.com/content/6/4/561.short
4100  - http://svn.bmj.com/content/6/4/561.full
SO  - Stroke Vasc Neurol2021 Dec 01; 6
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.