Cargando…

Semaphorin 3A Contributes to Secondary Blood–Brain Barrier Damage After Traumatic Brain Injury

Semaphorin 3A (SEMA3A) is a member of the Semaphorins family, a class of membrane-associated protein that participates in the construction of nerve networks. SEMA3A has been reported to affect vascular permeability previously, but its influence in traumatic brain injury (TBI) is still unknown. To in...

Descripción completa

Detalles Bibliográficos
Autores principales: Yang, Mengchen, Wang, Xiaoxue, Fan, Yueshan, Chen, Yaqing, Sun, Dongdong, Xu, Xin, Wang, Jianhao, Gu, Gang, Peng, Ruilong, Shen, Tianyu, Liu, Xilei, Li, Fanjian, Wang, Yi, Wang, Dong, Rong, Hongtao, Han, Zhenying, Gao, Xiangliang, Li, Qifeng, Fan, Keyuan, Yuan, Yuhua, Zhang, Jianning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444306/
https://www.ncbi.nlm.nih.gov/pubmed/30971898
http://dx.doi.org/10.3389/fncel.2019.00117
_version_ 1783408009516417024
author Yang, Mengchen
Wang, Xiaoxue
Fan, Yueshan
Chen, Yaqing
Sun, Dongdong
Xu, Xin
Wang, Jianhao
Gu, Gang
Peng, Ruilong
Shen, Tianyu
Liu, Xilei
Li, Fanjian
Wang, Yi
Wang, Dong
Rong, Hongtao
Han, Zhenying
Gao, Xiangliang
Li, Qifeng
Fan, Keyuan
Yuan, Yuhua
Zhang, Jianning
author_facet Yang, Mengchen
Wang, Xiaoxue
Fan, Yueshan
Chen, Yaqing
Sun, Dongdong
Xu, Xin
Wang, Jianhao
Gu, Gang
Peng, Ruilong
Shen, Tianyu
Liu, Xilei
Li, Fanjian
Wang, Yi
Wang, Dong
Rong, Hongtao
Han, Zhenying
Gao, Xiangliang
Li, Qifeng
Fan, Keyuan
Yuan, Yuhua
Zhang, Jianning
author_sort Yang, Mengchen
collection PubMed
description Semaphorin 3A (SEMA3A) is a member of the Semaphorins family, a class of membrane-associated protein that participates in the construction of nerve networks. SEMA3A has been reported to affect vascular permeability previously, but its influence in traumatic brain injury (TBI) is still unknown. To investigate the effects of SEMA3A, we used a mouse TBI model with a controlled cortical impact (CCI) device and a blood–brain barrier (BBB) injury model in vitro with oxygen-glucose deprivation (OGD). We tested post-TBI changes in SEMA3A, and its related receptors (Nrp-1 and plexin-A1) expression and distribution through western blotting and double-immunofluorescence staining, respectively. Neurological outcomes were evaluated by modified neurological severity scores (mNSSs) and beam-walking test. We examined BBB damage through Evans Blue dye extravasation, brain water content, and western blotting for VE-cadherin and p-VE-cadherin in vivo, and we examined the endothelial cell barrier through hopping probe ion conductance microscopy (HPICM), transwell leakage, and western blotting for VE-cadherin and p-VE-cadherin in vitro. Changes in miR-30b-5p were assessed by RT-PCR. Finally, the neuroprotective function of miR-30b-5p is measured by brain water content, mNSSs and beam-walking test. SEMA3A expression varied following TBI and peaked on the third day which expressed approximate fourfold increase compared with sham group, with the protein concentrated at the lesion boundary. SEMA3A contributed to neurological function deficits and secondary BBB damage in vivo. Our results demonstrated that SEMA3A level following OGD injury almost doubled than control group, and the negative effects of OGD injury can be improved by blocking SEMA3A expression. Furthermore, the expression of miR-30b-5p decreased approximate 40% at the third day and 60% at the seventh day post-CCI. OGD injury also exhibited an effect to approximately decrease 50% of miR-30b-5p expression. Additionally, the expression of SEMA3A post-TBI is regulated by miR-30b-5p, and miR-30b-5p could improve neurological outcomes post-TBI efficiently. Our results demonstrate that SEMA3A is a significant factor in secondary BBB damage after TBI and can be abolished by miR-30b-5p, which represents a potential therapeutic target.
format Online
Article
Text
id pubmed-6444306
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-64443062019-04-10 Semaphorin 3A Contributes to Secondary Blood–Brain Barrier Damage After Traumatic Brain Injury Yang, Mengchen Wang, Xiaoxue Fan, Yueshan Chen, Yaqing Sun, Dongdong Xu, Xin Wang, Jianhao Gu, Gang Peng, Ruilong Shen, Tianyu Liu, Xilei Li, Fanjian Wang, Yi Wang, Dong Rong, Hongtao Han, Zhenying Gao, Xiangliang Li, Qifeng Fan, Keyuan Yuan, Yuhua Zhang, Jianning Front Cell Neurosci Neuroscience Semaphorin 3A (SEMA3A) is a member of the Semaphorins family, a class of membrane-associated protein that participates in the construction of nerve networks. SEMA3A has been reported to affect vascular permeability previously, but its influence in traumatic brain injury (TBI) is still unknown. To investigate the effects of SEMA3A, we used a mouse TBI model with a controlled cortical impact (CCI) device and a blood–brain barrier (BBB) injury model in vitro with oxygen-glucose deprivation (OGD). We tested post-TBI changes in SEMA3A, and its related receptors (Nrp-1 and plexin-A1) expression and distribution through western blotting and double-immunofluorescence staining, respectively. Neurological outcomes were evaluated by modified neurological severity scores (mNSSs) and beam-walking test. We examined BBB damage through Evans Blue dye extravasation, brain water content, and western blotting for VE-cadherin and p-VE-cadherin in vivo, and we examined the endothelial cell barrier through hopping probe ion conductance microscopy (HPICM), transwell leakage, and western blotting for VE-cadherin and p-VE-cadherin in vitro. Changes in miR-30b-5p were assessed by RT-PCR. Finally, the neuroprotective function of miR-30b-5p is measured by brain water content, mNSSs and beam-walking test. SEMA3A expression varied following TBI and peaked on the third day which expressed approximate fourfold increase compared with sham group, with the protein concentrated at the lesion boundary. SEMA3A contributed to neurological function deficits and secondary BBB damage in vivo. Our results demonstrated that SEMA3A level following OGD injury almost doubled than control group, and the negative effects of OGD injury can be improved by blocking SEMA3A expression. Furthermore, the expression of miR-30b-5p decreased approximate 40% at the third day and 60% at the seventh day post-CCI. OGD injury also exhibited an effect to approximately decrease 50% of miR-30b-5p expression. Additionally, the expression of SEMA3A post-TBI is regulated by miR-30b-5p, and miR-30b-5p could improve neurological outcomes post-TBI efficiently. Our results demonstrate that SEMA3A is a significant factor in secondary BBB damage after TBI and can be abolished by miR-30b-5p, which represents a potential therapeutic target. Frontiers Media S.A. 2019-03-26 /pmc/articles/PMC6444306/ /pubmed/30971898 http://dx.doi.org/10.3389/fncel.2019.00117 Text en Copyright © 2019 Yang, Wang, Fan, Chen, Sun, Xu, Wang, Gu, Peng, Shen, Liu, Li, Wang, Wang, Rong, Han, Gao, Li, Fan, Yuan and Zhang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Yang, Mengchen
Wang, Xiaoxue
Fan, Yueshan
Chen, Yaqing
Sun, Dongdong
Xu, Xin
Wang, Jianhao
Gu, Gang
Peng, Ruilong
Shen, Tianyu
Liu, Xilei
Li, Fanjian
Wang, Yi
Wang, Dong
Rong, Hongtao
Han, Zhenying
Gao, Xiangliang
Li, Qifeng
Fan, Keyuan
Yuan, Yuhua
Zhang, Jianning
Semaphorin 3A Contributes to Secondary Blood–Brain Barrier Damage After Traumatic Brain Injury
title Semaphorin 3A Contributes to Secondary Blood–Brain Barrier Damage After Traumatic Brain Injury
title_full Semaphorin 3A Contributes to Secondary Blood–Brain Barrier Damage After Traumatic Brain Injury
title_fullStr Semaphorin 3A Contributes to Secondary Blood–Brain Barrier Damage After Traumatic Brain Injury
title_full_unstemmed Semaphorin 3A Contributes to Secondary Blood–Brain Barrier Damage After Traumatic Brain Injury
title_short Semaphorin 3A Contributes to Secondary Blood–Brain Barrier Damage After Traumatic Brain Injury
title_sort semaphorin 3a contributes to secondary blood–brain barrier damage after traumatic brain injury
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444306/
https://www.ncbi.nlm.nih.gov/pubmed/30971898
http://dx.doi.org/10.3389/fncel.2019.00117
work_keys_str_mv AT yangmengchen semaphorin3acontributestosecondarybloodbrainbarrierdamageaftertraumaticbraininjury
AT wangxiaoxue semaphorin3acontributestosecondarybloodbrainbarrierdamageaftertraumaticbraininjury
AT fanyueshan semaphorin3acontributestosecondarybloodbrainbarrierdamageaftertraumaticbraininjury
AT chenyaqing semaphorin3acontributestosecondarybloodbrainbarrierdamageaftertraumaticbraininjury
AT sundongdong semaphorin3acontributestosecondarybloodbrainbarrierdamageaftertraumaticbraininjury
AT xuxin semaphorin3acontributestosecondarybloodbrainbarrierdamageaftertraumaticbraininjury
AT wangjianhao semaphorin3acontributestosecondarybloodbrainbarrierdamageaftertraumaticbraininjury
AT gugang semaphorin3acontributestosecondarybloodbrainbarrierdamageaftertraumaticbraininjury
AT pengruilong semaphorin3acontributestosecondarybloodbrainbarrierdamageaftertraumaticbraininjury
AT shentianyu semaphorin3acontributestosecondarybloodbrainbarrierdamageaftertraumaticbraininjury
AT liuxilei semaphorin3acontributestosecondarybloodbrainbarrierdamageaftertraumaticbraininjury
AT lifanjian semaphorin3acontributestosecondarybloodbrainbarrierdamageaftertraumaticbraininjury
AT wangyi semaphorin3acontributestosecondarybloodbrainbarrierdamageaftertraumaticbraininjury
AT wangdong semaphorin3acontributestosecondarybloodbrainbarrierdamageaftertraumaticbraininjury
AT ronghongtao semaphorin3acontributestosecondarybloodbrainbarrierdamageaftertraumaticbraininjury
AT hanzhenying semaphorin3acontributestosecondarybloodbrainbarrierdamageaftertraumaticbraininjury
AT gaoxiangliang semaphorin3acontributestosecondarybloodbrainbarrierdamageaftertraumaticbraininjury
AT liqifeng semaphorin3acontributestosecondarybloodbrainbarrierdamageaftertraumaticbraininjury
AT fankeyuan semaphorin3acontributestosecondarybloodbrainbarrierdamageaftertraumaticbraininjury
AT yuanyuhua semaphorin3acontributestosecondarybloodbrainbarrierdamageaftertraumaticbraininjury
AT zhangjianning semaphorin3acontributestosecondarybloodbrainbarrierdamageaftertraumaticbraininjury