Bazedoxifene, a Selective Estrogen Receptor Modulator, Promotes Functional Recovery in a Spinal Cord Injury Rat Model

International Journal of Molecular Sciences

Hae Eun Shin¹  Eun Ji Roh¹  Seil Sohn¹  Su Yeon Kwon¹  Inbo Han¹  Hyemin Choi¹  Hari Prasad Joshi²  Yiyoung Kim³ 

[1] Department of Neurosurgery, CHA University School of Medicine, CHA Bundang Medical Center, Seongnam-si 13496, Gyeonggi-do, Korea;Department of Physiology and Pathophysiology, Spinal Cord Research Centre, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0W2, Canada;School of Medicine, CHA University, CHA Bundang Medical Center, Seongnam-si 13496, Gyeonggi-do, Korea;

关键词: spinal cord injury;    secondary injury;    inflammatory response;    remyelination;    bazedoxifene acetate;   

DOI  :  10.3390/ijms222011012

来源: DOAJ

【 摘 要 】

In research on various central nervous system injuries, bazedoxifene acetate (BZA) has shown two main effects: neuroprotection by suppressing the inflammatory response and remyelination by enhancing oligodendrocyte precursor cell differentiation and oligodendrocyte proliferation. We examined the effects of BZA in a rat spinal cord injury (SCI) model. Anti-inflammatory and anti-apoptotic effects were investigated in RAW 264.7 cells, and blood-spinal cord barrier (BSCB) permeability and angiogenesis were evaluated in a human brain endothelial cell line (hCMEC/D3). In vivo experiments were carried out on female Sprague Dawley rats subjected to moderate static compression SCI. The rats were intraperitoneally injected with either vehicle or BZA (1mg/kg pre-SCI and 3 mg/kg for 7 days post-SCI) daily. BZA decreased the lipopolysaccharide-induced production of proinflammatory cytokines and nitric oxide in RAW 264.7 cells and preserved BSCB disruption in hCMEC/D3 cells. In the rats, BZA reduced caspase-3 activity at 1 day post-injury (dpi) and suppressed phosphorylation of MAPK (p38 and ERK) at dpi 2, hence reducing the expression of IL-6, a proinflammatory cytokine. BZA also led to remyelination at dpi 20. BZA contributed to improvements in locomotor recovery after compressive SCI. This evidence suggests that BZA may have therapeutic potential to promote neuroprotection, remyelination, and functional outcomes following SCI.

【 授权许可】

Unknown