Up-regulation of microRNA-223 inhibits brain injury and hippocampal neuron apoptosis of rats after febrile seizure through the NLRP3-Caspase-1 signaling pathway
Authors: Bin Wang
Jie Lin
Xiangke Cao
Qingqiang Qian
Qingzeng Qian
Ling Yu
Journal: Biomedicine & Pharmacotherapy (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Brain injury; Febrile seizure; Hippocampal neurons; Inflammatory injury; Learning and memory ability
Affiliations: Department of Pediatrics, Affiliated Hospital of North China University of Science and Technology, Tangshan 063000, PR China., Experimental Center, School of Life Sciences, North China University of Science and Technology, Tangshan 063000, PR China., Department of Anesthesiology, Tangshan Maternal & Child Health Care Hospital, Tangshan 063000, PR China. Electronic address: ., Department of Neurology, Tangshan Workers' Hospital, Tangshan 063000, PR China., Experimental Center, School of Public Health, North China University of Science and Technology, Tangshan 063000, PR China.

Abstract:  Objective: This study is conducted to explore the role of microRNA-223 (miR-223) in brain injury and apoptosis of hippocampal neurons through the NLRP3-Caspase-1 signaling pathway in febrile seizure (FS) rats. Methods: The models of FS were induced in rats by hot water-bath, which were stereotactically injected with miR-223 mimics and mimics negative control (NC) to perturb the expression of miR-223. A series of experiments was conducted to find out the potential mechanisms of miR-223 on convulsion attack, learning and memory ability, pathological injury of hippocampal neurons, inflammatory injury, apoptosis of hippocampal neurons in FS rats. Besides, the targeting relationship between miR-223 and NLRP3 was also verified. Results: Low expression of miR-223 was found in hippocampus tissues of FS rats. Up-regulation of miR-223 alleviated convulsion attack and improved learning and memory ability, while inhibiting pathological injury of hippocampal neurons and inflammatory injury in FS rats. Up-regulation of miR-223 promoted the survival of hippocampal neurons and inhibited their apoptosis in FS rats. MiR-223 inhibited the activation of NLRP3-Caspase-1 signaling pathway in hippocampus tissues of FS rats by inhibiting NLRP3. Conclusion: The inhibited expression of miR-223 after FS may participate in the activation of the NLRP3-Caspase-1 signaling pathway, resulting in brain injury and apoptosis of hippocampal neurons in rat models of FS. 

Retracted: No

PubPeer comments:
 Fig 5A,  detection of hippocampal neuron survival in rats by Nissl staining . ![file] More repeated segments of texture than one would expect. ![file] Fig 5B,  detection of apoptosis in hippocampal neurons of rats by TUNEL staining . ![file] I have concerns. ![file] , 
 Fig 4B,  ultrastructure of hippocampal tissues of rats was observed by a transmission electron microscope . ![file] I have concerns. ![file] , 
 Fig 4A  the histopathology of hippocampal tissues of rats in each group was observed by HE staining . ![file] Unexpected repetitions. ![] ![] , 
 Fig 1B. ![file] Unexpected overlap with Fig 4A from  Micro RNA u2010140u20105p elevates cerebral protection of dexmedetomidine against hypoxicu2013ischaemic brain damage via the Wnt u03b2u2010catenin signalling pathway ([Han et al 2018] ) **[retracted]**. ![file] , 
 Figs 1A, 3B. ![file] Fig 2D. ![file] , 
 - *[left]* A panel from Fig 4 of Han et al (2018) **[retracted]**. - *[right]* Figs 3C, 5B. ![file] , 
 - *[left]* Fig 2C. - *[right]* Fig 2I from  Bactericidal Permeability-Increasing Protein Improves Cognitive Impairment in Diabetic Mice via Blockade of the LPS-LBP-TLR4 Signaling Pathway ([Sun et al 2021] ) **[retracted]**. Flipped through 180 deg for ease of comparison. ![file] ,