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Inflammation Research
Published in: Inflammation Research 4/2019

01-04-2019 | Central Nervous System Trauma | Original Research Paper

Bazedoxifene protects cerebral autoregulation after traumatic brain injury and attenuates impairments in blood–brain barrier damage: involvement of anti-inflammatory pathways by blocking MAPK signaling

Authors: Yu-Long Lan, Xun Wang, Yu-Jie Zou, Jin-Shan Xing, Jia-Cheng Lou, Shuang Zou, Bin-Bin Ma, Yan Ding, Bo Zhang

Published in: Inflammation Research | Issue 4/2019

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Abstract

Objective

Traumatic brain injury (TBI) is a significant cause of death and long-term deficits in motor and cognitive functions for which there are currently no effective chemotherapeutic drugs. Bazedoxifene (BZA) is a third-generation selective estrogen receptor modulator (SERM) and has been investigated as a treatment for postmenopausal osteoporosis. It is generally safe and well tolerated, with favorable endometrial and breast safety profiles. Recent findings have shown that SERMs may have therapeutic benefits; however, the role of BZA in the treatment of TBI and its molecular and cellular mechanisms remain poorly understood. The aim of the present study was to examine the neuroprotective effects of BZA on early TBI in rats and to explore the underlying mechanisms of these effects.

Materials and methods

TBI was induced using a modified weight-drop method. Neurological deficits were evaluated according to the neurological severity score (NSS). Morris water maze and open-field behavioral tests were used to test cognitive functions. Brain edema was measured by brain water content, and impairments in the blood–brain barrier (BBB) were evaluated by expression analysis of tight junction-associated proteins, such as occludin and zonula occludens-1 (ZO-1). Neuronal injury was assessed by hematoxylin and eosin (H&E) staining. LC–MS/MS analysis was performed to determine the ability of BZA to cross the BBB.

Results

Our results indicated that BZA attenuated the impaired cognitive functions and the increased BBB permeability of rats subjected to TBI through activation of inflammatory cascades. In vivo experiments further revealed that BZA provided this neuroprotection by suppressing TBI-induced activation of the MAPK/NF-κB signaling pathway. Thus, mechanically, the anti-inflammatory effects of BZA in TBI may be partially mediated by blocking the MAPK signaling pathway.

Conclusions

These findings suggest that BZA might attenuate neurological deficits and BBB damage to protect against TBI by blocking the MAPK/NF-κB signaling pathway.
Appendix
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Metadata
Title
Bazedoxifene protects cerebral autoregulation after traumatic brain injury and attenuates impairments in blood–brain barrier damage: involvement of anti-inflammatory pathways by blocking MAPK signaling
Authors
Yu-Long Lan
Xun Wang
Yu-Jie Zou
Jin-Shan Xing
Jia-Cheng Lou
Shuang Zou
Bin-Bin Ma
Yan Ding
Bo Zhang
Publication date
01-04-2019
Publisher
Springer International Publishing
Published in
Inflammation Research / Issue 4/2019
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-019-01217-z

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