Activation of AMPK improves lipopolysaccharide-induced dysfunction of the blood–brain barrier in mice
Authors: Zhan Liu
Yu-Bing Cai
Hai-Ya Yu
Journal: Brain Injury (2015)
Discipline: CLINICAL MEDICINE
Keywords: AMPK; Ageing; BBB; LPS; NAD(P)H oxidase
Affiliations: Department of Neurology,, Department of Otorhinolaryngology, The People’s Hospital of Xishui, Huang-Gang, Hubei, PR China, and, Department of Gastroenterology, People’s Hospital of Hunan Province, Hunan Normal University, Changsha, Hunan, PR China

Abstract:  Primary objective: Lipopolysaccharide (LPS) is known to alter the integrity of the blood-brain barrier (BBB) in sepsis, although the underlying mechanism remains unknown. The aim of this study was to elucidate the molecular mechanisms underlying disruption of the BBB in LPS-induced sepsis. Research design: Both in vitro and in vivo experiments were designed to test the role of AMP-activated protein kinase (AMPK) in LPS-induced BBB dysfunction. Methods and procedures: Human brain microvascular endothelial cells (HBMECs) were cultured. The protein expressions were detected by western blot. BBB integrity was determined by Evans Blue. Main outcomes and results: LPS (1 μg ml(-1)) dramatically increased the permeability of the BBB and the ROS productions, as well as reducing the expression levels of occludin and claudin-5 in cultured HBMECs. Inhibition of NAD(P)H oxidase by apocynin or up-regulation of AMPK reversed the LPS-induced abnormities in HBMECs. In LPS-induced sepsis in mice, it was found that LPS dramatically increased NAD(P)H oxidase protein expressions and ROS productions in the brain and disrupted BBB function assayed by Evans blue staining, which were abolished by AICAR treatment. Conclusions: It is concluded that AMPK activation improves the functions of the BBB impaired by LPS through suppression of NAD(P)H oxidase-derived ROS in mice. 

Retracted: Yes

PubPeer comments:
 Retracted [July 2018] . ------------------------------------------------------------ We, the Editor and Publisher of Brain Injury, have retracted the following manuscript that was posted online on 20 March 2015: Hai-Ya Yu, Yu-Bing Cai Zhan Liu, u201cActivation of AMPK improves lipopolysaccharide-induced dysfunction of the bloodu2013brain barrier in miceu201d DOI: 10.3109 02699052.2015.1004746. Brain Injury. This article has been retracted due to duplication of Western Blot (GAPDH) figures (Fig-6b) and duplication of text from the previously published, Zhihong Zhao, Jue Hu, Xiaoping Gao, Hui Liang, Zhan Liu, u201cActivation of AMPK attenuates lipopolysaccharide-impaired integrity and function of bloodu2013brain barrier in human brain microvascular endothelial cellsu201d DOI: S0014480014001476. *Experimental and Molecular Pathology*. Taylor Francis notes that we received, peer-reviewed, accepted, and published the article in good faith. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as RETRACTED. ---------------------------------------------- Further overlaps were documented by the Editors of PLoS in their retraction note for [Zhao et al (2014)] . , 
 Western blots and some other figure panels in this paper are strikingly similar to panels found in other, seemingly unrelated papers, with different sets of authors and institutions. The panels do not represent the same proteins or experiments. All papers in this set (18 identified so far) are connected to each other by the same Western blots, graphs, or microscopy photos. These papers might all have been prepared by the same external company, as admitted by the authors in the now retracted paper Long Zhao et al., PLOS ONE (2014), DOl: 10.1371 journal.pone.0113398 - https: pubpeer.com publications 29F5C2BCC1C389A566BB106F3F825C, which is part of this set. For now, I will call this the [External Company Paper Mill.] Some images from this set of papers appeared first in papers by Shuangxi Wang, Ping Song, and Ming-Hui Zou published around 2007-2012. Multiple papers from these three authors are also cited in most of the papers in this paper mill, sometimes constituting 10% of all references or more. This might suggest that this paper mill might have been set up for citation boosting. Here is Figure 3C from this paper and that of three others in this set. Boxes of the same color highlight immunoblots that look remarkably similar, although they are sometimes shown in mirror image. Note also the similarities between the bar graphs in the same figures. ![file] ,