Alleviation of glutamate mediated neuronal insult by piroxicam in rodent model of focal cerebral ischemia: a possible mechanism of GABA agonism
Authors: Pallab Bhattacharya
Sudip Paul
Ranjana Patnaik
Anand Kumar Pandey
Journal: Journal of Physiology and Biochemistry (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Neurotransmitter imbalance; cerebral ischemia; piroxicam; glutamate; GABA
Affiliations: Department of Neurology, Leonard M. Miller School of Medicine, Miami, FL, 33136, USA, .

Abstract:  Neurotransmitter imbalance is an inevitable outcome in cerebral ischemia that leads to neuronal death. In the present study, we evaluated the effects of piroxicam, a nonsteroidal anti-inflammatory drug (NSAID), on extracellular brain glutamate and γ-aminobutyric acid (GABA) release, survival time, and neuronal cell death. Transient focal cerebral ischemia in male Charles Foster rat led to neuronal infarction and compromised intrinsic antioxidant status. Thirty-minute preadministration of piroxicam (10 mg/kg b.w.) showed a significant (P &lt; 0.01) reduction in cerebral infarct volume and potentiation of the intrinsic antioxidant status. High-performance liquid chromatography of brain cortex and striatum revealed changes in extracellular concentrations of neurotransmitters which were found to be 0.519 ± 0.44 pmole/mg (GABA); 1.18 ± 0.28 pmole/mg (glutamate), and 0.63 ± 0.21 pmole/mg (serotonin), respectively. Hydroxyl radical (·OH) adduct of salicylate in the frontal cortex and striatum in control, untreated, and treated groups was found to be 0.261 ± 0.06, 0.68 ± 0.52, and 0.401 ± 0.68 pmole/mg, respectively. After stroke, the extracellular level of glutamate in rat brain increases continuously as compared to that of control group. However, piroxicam administration in stroke rat significantly reduced (P &lt; 0.05) elevated extracellular cerebral glutamate. This indicates that piroxicam attenuates extracellular glutamate release and also reduces neuronal cell death due to reduction in oxidative stress in cerebral ischemia. Our results also indicate a consequent increase of extracellular GABA in brain regions administered with piroxicam, which hints that piroxicam alleviates glutamate excitotoxicity possibly by GABA agonism. 

Retracted: Yes

PubPeer comments:
 Fig. 2 2,3,5-Triphenyltetrazolium chloride (TTC) staining for detection of brain infarct and functional assessments by neurological deficit scoring. a TTC-stained coronal brain sections of control, untreated, and treated rats. Images recycled from previous publications of authors. Different treatment but similar images? ![file] , 
 Images do not look similar. TTC stains are always confusing looking similar in context to its small pattern of infarct and volume .This can only be clearly differentiated when you see the original data file. It will rechecked with the raw data file and if any misupload has mistakenly happened will surely communicate to journal for correction.This doesnot affect the main findings of the study anyways .Thank you for your time. As an supporting author of this paper, this is my observation. , 
 #2 Unfortunately, I concur with the concerns expressed in #1. The fact that u201cImages do not look similaru201d is only due to the fact that the image dimensions have been altered. The authors are advised to correct the scientific record by correcting or withdrawing the duplicated images paper. Further protestations here will not convince experienced readers. , 
 #3 Comparisons are easier after rescaling the images. ![file] , 
 I appreciate your response. However, the images have the same shade, same infarct area and same background shadows. Please share raw data images in support of your observation.![file] , 
 In the interests of avoiding a lengthy and largely repetitive reply in one way or other, I am going to refrain from further posts on this topic. I do genuinely appreciate being made us aware of this and assure you that we will check this at our end and will do needful that will be required.I certainly donu2019t claim to be perfect and am happy to 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  Journal of Physiology and Biochemistry  or  Plos One . The above image panel published in  Journal of Physiology and Biochemistry 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. Image in below comment. , 
 ![file] , 
  08 September 2020 Editor s Note: Concerns have been raised about the integrity of the data reported in this article (Bhattacharya et al., 2014). This is currently being investigated. Further editorial action may be taken as appropriate once the investigation into the concerns is complete and all parties have been given an opportunity to respond in full. It would seem that despite the internet being a  challenging venue that one year is sufficient time to resolve the problems outlined above. [Other papers with concerns] have been resolved by now. , 
 Retracted [5 April 2022] . ------------------- The Editors-in-Chief have retracted this article because of anomalies in the images of brain sections presented in Figure 2a, namely: - 7 panels in Figure 2a appear to be the same as panels in Figure 2a of a previous article [1] - 2 panels in Figure 2a appear to be the same as panels in Figure 2a of a previous article [2] - 2 panels in Figure 2a appear to be the same as panels in Figure 2a and 1 panel appears to be the same as a panel in Figure 3a of a previous article [3] - 5 panels in Figure 2a appear to be the same as panels in Figure 2C of a previous article [4] The Editors-in-Chief therefore no longer have confidence in the results and conclusions presented. Pallab Bhattacharya, Anand Kumar Pandey, Sudip Paul and Ranjana Patnaik disagree with this retraction. References - [1] Retracted article: Bhattacharya P, Pandey AK, Paul S, Patnaik R, Yavagal DR (2013) Aquaporin-4 inhibition mediates piroxicam-induced neuroprotection against focal cerebral ischemia reperfusion injury in rodents. PLoS ONE 8(9):e73481 - [2 ] Retracted article: Pandey AK, Hazari PP, Patnaik R, Mishra AK (2011) The role of ASIC1a in neuroprotection elicited by quercetin in focal cerebral ischemia. Brain Res 1383:289u2013299 - [3] Retracted article: Bhattacharya P, Pandey AK, Paul S, Patnaik R (2014) Melatonin renders neuroprotection by protein kinase C mediated aquaporin-4 inhibition in animal model of focal cerebral ischemia. Life Sci 100(2):97u2013109 - [4] Mishra V, Verma R, Raghubir R (2010) Neuroprotective effect of flurbiprofen in focal cerebral ischemia: the possible role of ASIC1a. Neuropharmacology 59(7u20138):582u2013588 , 
 See also https: retractionwatch.com 2022 05 24 the-internet-may-be-a-challenging-venue-biomedical-engineering-group-up-to-four-retractions ,