MicroRNA-152 attenuates neuroinflammation in intracerebral hemorrhage by inhibiting thioredoxin interacting protein (TXNIP)-mediated NLRP3 inflammasome activation |
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| Institution: | 1. Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang 110000, People’s Republic of China;2. Department of Neurology, The First Affiliated Hospital Sun Yat-sen University, Guangzhou 510080, People’s Republic of China;3. Department of Tissue Engineering, China Medical University, Shenyang 110122, People’s Republic of China;1. Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, China;2. Institute of Brain Science, Harbin Medical University, Harbin, China;3. Bashkir State Medical University, Ufa, Russia;1. Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China;2. Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China;3. Department of Neurosurgery, Guangdong General Hospital, Guangzhou, Guangdong 510080, China;4. Neuroscience and Neuroengineering Research Center, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200025, China;5. Department of Neurosurgery, Ruijin Hospital Luwan Branch, Shanghai Jiao Tong University, School of Medcine, Shanghai 200025, China;1. Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China;2. Department of Emergency, The First Affiliated Hospital of Zunyi Medical College, Guizhou 563003, China;1. Department of Rehabilitation Medicine, Yongchuan Hospital, Chongqing Medical University, Chongqing, 402160, China;2. Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, 402160, China;1. Halifax Medical Center, 303N. Clyde Morris Blvd, Daytona Beach, FL 32114, USA;2. University of Rome La Sapienza, Anesthesia, Piazzale Aldo Moro 5, Rome 00185, Italy;3. New York Institute of Technology College of Osteopathic Medicine, Medicine, 101 Northern Blv, Glen Head, NY 11545, USA;4. Ain Shams University, Intensive Care Medicine, 38 Abbassia, By Al-Nour Mosque, Cairo 62111, Egypt;5. University of Florida, Neurosurgery, 303N Clyde Morris Blvd, Suite 550-560, Daytona Beach, FL 32114, USA;6. Beni Suef University, Faculty of Medicine, Neurosurgery, Mohamed Hassan Street, Beni Suef, Egypt |
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| Abstract: | Neuroinflammation significantly contributes to brain injury and neurological deterioration following intracerebral hemorrhage (ICH). MicroRNA-152(miR-152) was reported to be downregulated in ICH patients and to possess anti-inflammatory properties in other diseases. In this study, we aimed to explore the role of miR-152 in ICH, and the underlying mechanisms, using a collagenase-induced rat ICH model and hemin-exposure as a cell model. We first confirmed that miR-152 was consistently downregulated in both models. Overexpression of miR-152 in microglial BV2 cells reduced hemin-induced inflammatory response and reactive oxygen species (ROS) generation, thus protecting co-cultured neuronal HT22 cells. Moreover, overexpression of miR-152 by intracerebroventricular lentivirus injection in ICH rats significantly alleviated neurodecifits, brain edema, and hematoma. These changes were associated with a marked reduction in ICH-induced neuronal death, as detected by co-staining of NeuN and TUNEL, and ICH-induced neuroinflammation, as revealed by inflammatory cytokine levels as well as by the number of Iba1 positive-stained cells in the perihematomal region. Mechanistically, miR-152 significantly inhibited ICH-induced TXNIP expression, and its overexpression blocked the interaction between TXNIP and NOD-like receptor pyrin domain containing 3(NLRP3), thus inhibiting NLRP3-driven inflammasome activation to attenuate neuroinflammation in vivo and in vitro. Moreover, the results of si-TXNIP transfection further confirmed that TXNIP inhibition was involved in the reduction of NLRP3 inflammasome activation by the overexpression of miR-152. Collectively, the present study demonstrates that miR-152 confers protection against ICH-induced neuroinflammation and brain injury by inhibiting TXNIP-mediated NLRP3 inflammasome activation, indicating a potential strategy for ICH treatment. |
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| Keywords: | Intracerebral hemorrhage Neuroinflammation MicroRNA-152 TXNIP NLRP3 inflammasome |
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