Plasma from healthy donors protects blood–brain barrier integrity via FGF21 and improves the recovery in a mouse model of cerebral ischaemia
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 adul...
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| Series: | Stroke and Vascular Neurology |
| Online Access: | https://svn.bmj.com/content/early/2021/03/30/svn-2020-000774.full |
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doaj-769a1270b78a4ddeb345573aa88f52262021-04-03T16:30:03ZengBMJ Publishing GroupStroke and Vascular Neurology2059-869610.1136/svn-2020-000774Plasma from healthy donors protects blood–brain barrier integrity via FGF21 and improves the recovery in a mouse model of cerebral ischaemiaHui Shen0Chang Liu1Guo-Yuan Yang2Zhijun Zhang3Yongfang Li4Yaohui Tang5Muyassar Mamtilahun6Lu Jiang7Yaying Song8Xiaojing Shi9Yixu Jiang10Lidong Deng11Haoran Zheng12Yongting Wang13Neuroscience and Neuroengineering Center, Shanghai Jiao Tong University School of Biomedical Engineering, Shanghai, ChinaNeuroscience and Neuroengineering Center, Shanghai Jiao Tong University School of Biomedical Engineering, Shanghai, ChinaNeuroscience and Neuroengineering Center, Shanghai Jiao Tong University School of Biomedical Engineering, Shanghai, ChinaNeuroscience and Neuroengineering Center, Shanghai Jiao Tong University School of Biomedical Engineering, Shanghai, ChinaDepartment of Neurology, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, ChinaNeuroscience and Neuroengineering Center, Shanghai Jiao Tong University School of Biomedical Engineering, Shanghai, ChinaNeuroscience and Neuroengineering Center, Shanghai Jiao Tong University School of Biomedical Engineering, Shanghai, ChinaNeuroscience and Neuroengineering Center, Shanghai Jiao Tong University School of Biomedical Engineering, Shanghai, ChinaNeuroscience and Neuroengineering Center, Shanghai Jiao Tong University School of Biomedical Engineering, Shanghai, ChinaNeuroscience and Neuroengineering Center, Shanghai Jiao Tong University School of Biomedical Engineering, Shanghai, ChinaNeuroscience and Neuroengineering Center, Shanghai Jiao Tong University School of Biomedical Engineering, Shanghai, ChinaNeuroscience and Neuroengineering Center, Shanghai Jiao Tong University School of Biomedical Engineering, Shanghai, ChinaNeuroscience and Neuroengineering Center, Shanghai Jiao Tong University School of Biomedical Engineering, Shanghai, ChinaNeuroscience and Neuroengineering Center, Shanghai Jiao Tong University School of Biomedical Engineering, Shanghai, ChinaBackground 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.https://svn.bmj.com/content/early/2021/03/30/svn-2020-000774.full |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Hui Shen Chang Liu Guo-Yuan Yang Zhijun Zhang Yongfang Li Yaohui Tang Muyassar Mamtilahun Lu Jiang Yaying Song Xiaojing Shi Yixu Jiang Lidong Deng Haoran Zheng Yongting Wang |
| spellingShingle |
Hui Shen Chang Liu Guo-Yuan Yang Zhijun Zhang Yongfang Li Yaohui Tang Muyassar Mamtilahun Lu Jiang Yaying Song Xiaojing Shi Yixu Jiang Lidong Deng Haoran Zheng Yongting Wang Plasma from healthy donors protects blood–brain barrier integrity via FGF21 and improves the recovery in a mouse model of cerebral ischaemia Stroke and Vascular Neurology |
| author_facet |
Hui Shen Chang Liu Guo-Yuan Yang Zhijun Zhang Yongfang Li Yaohui Tang Muyassar Mamtilahun Lu Jiang Yaying Song Xiaojing Shi Yixu Jiang Lidong Deng Haoran Zheng Yongting Wang |
| author_sort |
Hui Shen |
| title |
Plasma from healthy donors protects blood–brain barrier integrity via FGF21 and improves the recovery in a mouse model of cerebral ischaemia |
| title_short |
Plasma from healthy donors protects blood–brain barrier integrity via FGF21 and improves the recovery in a mouse model of cerebral ischaemia |
| title_full |
Plasma from healthy donors protects blood–brain barrier integrity via FGF21 and improves the recovery in a mouse model of cerebral ischaemia |
| title_fullStr |
Plasma from healthy donors protects blood–brain barrier integrity via FGF21 and improves the recovery in a mouse model of cerebral ischaemia |
| title_full_unstemmed |
Plasma from healthy donors protects blood–brain barrier integrity via FGF21 and improves the recovery in a mouse model of cerebral ischaemia |
| title_sort |
plasma from healthy donors protects blood–brain barrier integrity via fgf21 and improves the recovery in a mouse model of cerebral ischaemia |
| publisher |
BMJ Publishing Group |
| series |
Stroke and Vascular Neurology |
| issn |
2059-8696 |
| description |
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. |
| url |
https://svn.bmj.com/content/early/2021/03/30/svn-2020-000774.full |
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