RETRACTED: Melatonin renders neuroprotection by protein kinase C mediated aquaporin-4 inhibition in animal model of focal cerebral ischemia
Authors: Pallab Bhattacharya
Sudip Paul
Ranjana Patnaik
Anand Kumar Pandey
Journal: Life Sciences (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Aquaporin-4; Brain edema; Melatonin; Neuroprotection; Protein kinase C.
Affiliations: Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136, USA; School of Biomedical Engineering, Indian Institute of Technology, Banaras Hindu University, Varanasi 221005, UP, India. Electronic address: ., School of Biomedical Engineering, Indian Institute of Technology, Banaras Hindu University, Varanasi 221005, UP, India., School of Biomedical Engineering, Indian Institute of Technology, Banaras Hindu University, Varanasi 221005, UP, India; Department of Biomedical Engineering, North Eastern Hill University (NEHU), Shillong, 793022, Meghalaya, India.

Abstract:  Aim: Aquaporin-4(AQP4) expression in the brain with relation to edema formation following focal cerebral ischemia was investigated. Studies have shown that brain edema is one of the significant factors in worsening stroke outcomes. While many mechanisms may aggravate brain injury, one such potential system may involve AQP4 up regulation in stroke patients that could result in increased edema formation. Post administration of melatonin following ischemic stroke reduces AQP4 mediated brain edema and confers neuroprotection. Materials and methods: An in-silico approach was undertaken to confirm effective melatonin-AQP4 binding. Rats were treated with 5mg/kg, i.p. melatonin or placebo at 30 min prior, 60 min post and 120 min post 60 min of middle cerebral artery occlusion (MCAO) followed by 24h reperfusion. Rats were evaluated for battery of neurological and motor function tests just before sacrifice. Brains were harvested for infarct size estimation, water content measurement, biochemical analysis, apoptosis study and western blot experiments. Key findings: Melatonin at 60 min post ischemia rendered neuroprotection as evident by reduction in cerebral infarct volume, improvement in motor and neurological deficit and reduction in brain edema. Furthermore, ischemia induced surge in levels of nitrite and malondialdehyde (MDA) were also found to be significantly reduced in ischemic brain regions in treated animals. Melatonin potentiated intrinsic antioxidant status, inhibited acid mediated rise in intracellular calcium levels, decreased apoptotic cell death and also markedly inhibited protein kinase C (PKC) influenced AQP4 expression in the cerebral cortex and dorsal striatum. Significance: Melatonin confers neuroprotection by protein kinase C mediated AQP4 inhibition in ischemic stroke. 

Retracted: Yes

PubPeer comments:
 Fig. 2. Effect of different doses of melatonin treatment on (a) TTC stained coronal brain sections of sham, vehicle and melatonin treated rats. and Fig 3 Effect of melatonin (5 mg kg) pre and post treatment on (a) TTC stained coronal brain sections of sham, vehicle and melatonin treated rats The TTC images seem to be the same images published by the authors in their Plos One paper. How could different treatment yield similar images?![file] , 
 I do genuinely appreciate your time and assure you that the needful has been done.We certainly can engage in good faith dialogue about our work, but the internet may be a challenging venue when investigations are underway. , 
 The  Plos One article with similar images now stands retracted however enigma still remains that whether the images belong to the research published in  Life Sciences or  Plos One . The above image panel published in  Life Sciences seems to have some images similar to the images published in an article in  Neuropharmacology in 2010 . The article published in  Neuropharmacology has images in black and white, while the color images were provided by the authors . Interestingly, the  Plos One retraction mentions this very same article from  Neuropharmacology in their retraction statement. ![file] . , 
 2021 retraction. https: www.sciencedirect.com science article pii S0024320521001946?via%3Dihub This article has been retracted at the request of the Editor-in-Chief. Panels from Figures 2a and 3a appear similar to panels from Figures 2A and 3A of the article that the authors et al. have previously published in PLoS One 8(9) (2013) e73481 https: doi.org 10.1371 journal.pone.0073481 and Figures 1c and 2c of the article that Vikas Mishra, Rajkumar Verma and Ram Raghubir have published in Neuropharmacology 59 (2010) 582-588 https: doi.org 10.1016 j.neuropharm.2010.08.015. One of the conditions of submission of a paper for publication is that authors declare explicitly that the work is original. Re-use of any data should be appropriately cited. As such this article represents a misuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process. , 
 See also https: retractionwatch.com 2022 05 24 the-internet-may-be-a-challenging-venue-biomedical-engineering-group-up-to-four-retractions ,