International Journal of Biological Sciences

Impact factor

ISSN 1449-2288

News feeds of IJBS published articles
Manuscript login

open access Global reach, higher impact

Journal of Genomics - Submit manuscript now...


International Journal of Medical Sciences

Journal of Cancer

Journal of Genomics



Journal of Biomedicine

PubMed Central Indexed in Journal Impact Factor

Int J Biol Sci 2017; 13(12):1520-1531. doi:10.7150/ijbs.21107

Research Paper

Dl-3-n-butylphthalide prevents the disruption of blood-spinal cord barrier via inhibiting endoplasmic reticulum stress following spinal cord injury

Binbin Zheng1,2,3*, Yulong Zhou2,3*, Hongyu Zhang3, Guangyong Yang1, Zhenghua Hong1, Dandan Han1, Qingqing Wang2, Zili He2, Yanlong Liu3, Fenzan Wu4, Xie Zhang5, Songlin Tong4, Huazi Xu2✉, Jian Xiao3✉

1. Department of Orthopaedics, Taizhou Hospital, Wenzhou Medical University, Linhai, Zhejiang, 317000 PR China;
2. Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325035 PR China;
3. Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, 325035 PR China;
4. Department of Neurosurgery, Affiliated Cixi People's Hospital, Wenzhou Medical University, Ningbo, Zhejiang, 315300, PR China;
5. Department of Gastroenterology, Ningbo Medical Treatment Center Li Hui-li Hospital, Ningbo, Zhejiang, 315040, PR China.
* These authors had equal contribution and are designated as co-first authors.


After spinal cord injury (SCI), the destruction of blood-spinal cord barrier (BSCB) is shown to accelerate gathering of noxious blood-derived components in the nervous system, leading to secondary neurodegenerative damages. SCI activates endoplasmic reticulum stress (ER stress), which is considered to evoke secondary damages of neurons and glia. Recent evidence indicates that Dl-3-n-butylphthalide (NBP) has the neuroprotective effect in ischaemic brain injury, but whether it has protective effects on SCI or not is largely unclear. Here, we show that NBP prevented BSCB disruption after SCI via inhibition of ER stress. Following a moderate contusion injury of the T9 level of spinal cord, NBP was administered by oral gavage and further treated once a day. NBP significantly attenuated BSCB permeability and breakdown of adherens junction (AJ) and tight junction (TJ) proteins, then improved locomotion recovery following SCI. The protective role of NBP on BSCB disruption is associated with the restrain of ER stress caused by SCI. Furthermore, NBP considerably constrained the expression of ER stress-associated proteins and degradation of TJ and AJ in human brain microvascular endothelial cells (HBMECs) treated with TG. In conclusion, our results indicate that ER stress is associated with the disruption of BSCB integrity after injury, NBP attenuates BSCB disruption via inhibiting ER stress and improve functional recovery following SCI.

Keywords: Dl-3-n-butylphthalide, Blood-spinal cord barrier, Spinal cord injury, Endocytoplasmic reticulum stress.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( See for full terms and conditions.
How to cite this article:
Zheng B, Zhou Y, Zhang H, Yang G, Hong Z, Han D, Wang Q, He Z, Liu Y, Wu F, Zhang X, Tong S, Xu H, Xiao J. Dl-3-n-butylphthalide prevents the disruption of blood-spinal cord barrier via inhibiting endoplasmic reticulum stress following spinal cord injury. Int J Biol Sci 2017; 13(12):1520-1531. doi:10.7150/ijbs.21107. Available from