Celastrol inhibits microglial pyroptosis and attenuates inflammatory reaction in acute spinal cord injury rats |
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| Institution: | 1. Department of Neurosurgery, Gyeongsang National University, Gyeongsang National University Hospital, Jinju, Republic of Korea;2. Department of Neurosurgery, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea;3. Department of Neurosurgery, Seoul National University Hospital, Seoul, Republic of Korea;4. Department of Neurosurgery, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, 03080 Seoul, South Korea;5. Department of Neurosurgery, CHA University, CHA Bundang Medical Center, Seongnam-si, Gyeonggido, Republic of Korea;1. Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002 Jiangsu, China;2. The Center of Diagnosis and Treatment for Joint Disease, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University, China;3. MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, China;1. Department of Rehabilitation Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, People''s Republic of China;2. Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang 110122, People''s Republic of China |
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| Abstract: | Pyroptosis pathway is closely related to inflammation. However, Celastrol effect on pyroptosis pathway after spinal cord injury (SCI) are poorly understood. We studied the anti-inflammatory and neuroprotective effects of Celastrol on acute spinal cord injury in rats, and its anti-inflammatory effects on lipopolysaccharide (LPS)/ATP-induced microgliosis. Our results show that Celastrol can improve the recovery of hindlimb motor function after SCI in Sprague-Dawley (SD) rats, and reduce the cavity area of spinal cord injury along with the neuronal loss. Celastrol simultaneously reduced the activation of microglia (especially M1 microglia) in the spinal cord, inhibited the pyroptosis-related proteins (NLRP3 ASC Caspase-1 GSDMD), reduced the release of TNF-α IL-1β and IL-18 inflammatory factors, and increased the release of IL10 cytokines. In vitro studies showed that Celastrol reduced the toxicity resulting from the administration of LPS with ATP to BV-2 cells, inhibited the pyroptosis-related proteins (NLRP3 Caspase-1 GSDMD), and inhibited the release of corresponding inflammatory factors. Finally, Celastrol can inhibit the expression of NFκB/p-p65 in vitro and in vivo. Our results show that Celastrol can attenuate the inflammatory response of the spinal cord after SCI, which is associated with inhibition of microglial activation and pyroptosis pathway. Further study to explore the use of Celastrol to treat SCI is warranted. |
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