Frontiers in Cellular Neuroscience (Mar 2019)
Semaphorin 3A Contributes to Secondary Blood–Brain Barrier Damage After Traumatic Brain Injury
- Mengchen Yang,
- Mengchen Yang,
- Mengchen Yang,
- Xiaoxue Wang,
- Xiaoxue Wang,
- Yueshan Fan,
- Yueshan Fan,
- Yueshan Fan,
- Yaqing Chen,
- Yaqing Chen,
- Dongdong Sun,
- Dongdong Sun,
- Dongdong Sun,
- Xin Xu,
- Xin Xu,
- Xin Xu,
- Jianhao Wang,
- Jianhao Wang,
- Jianhao Wang,
- Gang Gu,
- Gang Gu,
- Gang Gu,
- Ruilong Peng,
- Ruilong Peng,
- Ruilong Peng,
- Tianyu Shen,
- Tianyu Shen,
- Xilei Liu,
- Xilei Liu,
- Xilei Liu,
- Fanjian Li,
- Fanjian Li,
- Fanjian Li,
- Yi Wang,
- Yi Wang,
- Dong Wang,
- Dong Wang,
- Hongtao Rong,
- Hongtao Rong,
- Zhenying Han,
- Zhenying Han,
- Xiangliang Gao,
- Xiangliang Gao,
- Xiangliang Gao,
- Qifeng Li,
- Qifeng Li,
- Qifeng Li,
- Keyuan Fan,
- Yuhua Yuan,
- Yuhua Yuan,
- Jianning Zhang,
- Jianning Zhang,
- Jianning Zhang
Affiliations
- Mengchen Yang
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
- Mengchen Yang
- Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China
- Mengchen Yang
- Tianjin Medical University, Tianjin, China
- Xiaoxue Wang
- Tianjin Medical University, Tianjin, China
- Xiaoxue Wang
- Department of Clinical Laboratory Diagnostics, Tianjin Medical University General Hospital, Tianjin, China
- Yueshan Fan
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
- Yueshan Fan
- Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China
- Yueshan Fan
- Tianjin Medical University, Tianjin, China
- Yaqing Chen
- Tianjin Medical University, Tianjin, China
- Yaqing Chen
- Department of Clinical Laboratory Diagnostics, Tianjin Medical University General Hospital, Tianjin, China
- Dongdong Sun
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
- Dongdong Sun
- Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China
- Dongdong Sun
- Tianjin Medical University, Tianjin, China
- Xin Xu
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
- Xin Xu
- Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China
- Xin Xu
- Tianjin Medical University, Tianjin, China
- Jianhao Wang
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
- Jianhao Wang
- Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China
- Jianhao Wang
- Tianjin Medical University, Tianjin, China
- Gang Gu
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
- Gang Gu
- Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China
- Gang Gu
- Tianjin Medical University, Tianjin, China
- Ruilong Peng
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
- Ruilong Peng
- Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China
- Ruilong Peng
- Tianjin Medical University, Tianjin, China
- Tianyu Shen
- Tianjin Medical University, Tianjin, China
- Tianyu Shen
- The Second Hospital of Tianjin Medical University, Tianjin, China
- Xilei Liu
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
- Xilei Liu
- Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China
- Xilei Liu
- Tianjin Medical University, Tianjin, China
- Fanjian Li
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
- Fanjian Li
- Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China
- Fanjian Li
- Tianjin Medical University, Tianjin, China
- Yi Wang
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
- Yi Wang
- Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China
- Dong Wang
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
- Dong Wang
- Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China
- Hongtao Rong
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
- Hongtao Rong
- Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China
- Zhenying Han
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
- Zhenying Han
- Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China
- Xiangliang Gao
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
- Xiangliang Gao
- Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China
- Xiangliang Gao
- Tianjin Medical University, Tianjin, China
- Qifeng Li
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
- Qifeng Li
- Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China
- Qifeng Li
- Tianjin Medical University, Tianjin, China
- Keyuan Fan
- Tianjin Chest Hospital, Tianjin, China
- Yuhua Yuan
- Tianjin Medical University, Tianjin, China
- Yuhua Yuan
- Department of Clinical Laboratory Diagnostics, Tianjin Medical University General Hospital, Tianjin, China
- Jianning Zhang
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
- Jianning Zhang
- Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China
- Jianning Zhang
- Tianjin Medical University, Tianjin, China
- DOI
- https://doi.org/10.3389/fncel.2019.00117
- Journal volume & issue
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Vol. 13
Abstract
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.
Keywords