Hongpeng Li1, Qin Zhang2, Xiaohui Yang3, Liping Wang4. 1. Yuncheng Central Hospital, Shanxi 044000, PR China; Department of Emergency and Critical Care Medicine, Zhoupu Hospital affiliated with Shanghai University of Medicine and Health Sciences, Shanghai 201318, PR China. Electronic address: liroc119@163.com. 2. Yuncheng Central Hospital, Shanxi 044000, PR China. Electronic address: zhangqin19762@126.com. 3. Yuncheng Central Hospital, Shanxi 044000, PR China. 4. Second Hospital of Lanzhou University, Gansu 730000, PR China.
Abstract
BACKGROUND: Secondary damage is often more important in determining the functional outcome and provides a practical target for therapeutic intervention. Rosiglitazone (ROSG) is a potent PPAR-γ agonist and has been shown to induce neuroprotection in animal models of spinal cord injury (SCI). However, it is still unclear whether this PPAR-γ agonist can mediate neuronal autophagy after SCI. METHODS: SCI was induced by application of vascular clips (force of 24g) to the dura via a four-level T5-T8 laminectomy. The role of the PPAR-γ agonist ROSG on neuronal autophagy induced by SCI was investigated. RESULTS: The expression of autophagy-related proteins, including microtubule-associated protein 1 light chain 3 type II (LC3-II), beclin-1, and cathepsin D, increased significantly after SCI. ROSG downregulated autophagy-related protein expression and improved the locomotor function after SCI. GW9662 (a PPAR-γ inhibitor) significantly antagonized the effect of ROSG and abolished the protective effect on SCI. CONCLUSIONS: Our results clearly demonstrated that the administration of ROSG after SCI reduced autophagy and promoted functional recovery after SCI in rats.
BACKGROUND: Secondary damage is often more important in determining the functional outcome and provides a practical target for therapeutic intervention. Rosiglitazone (ROSG) is a potent PPAR-γ agonist and has been shown to induce neuroprotection in animal models of spinal cord injury (SCI). However, it is still unclear whether this PPAR-γ agonist can mediate neuronal autophagy after SCI. METHODS: SCI was induced by application of vascular clips (force of 24g) to the dura via a four-level T5-T8 laminectomy. The role of the PPAR-γ agonist ROSG on neuronal autophagy induced by SCI was investigated. RESULTS: The expression of autophagy-related proteins, including microtubule-associated protein 1 light chain 3 type II (LC3-II), beclin-1, and cathepsin D, increased significantly after SCI. ROSG downregulated autophagy-related protein expression and improved the locomotor function after SCI. GW9662 (a PPAR-γ inhibitor) significantly antagonized the effect of ROSG and abolished the protective effect on SCI. CONCLUSIONS: Our results clearly demonstrated that the administration of ROSG after SCI reduced autophagy and promoted functional recovery after SCI in rats.
Authors: Antony Justin; Subhankar Mandal; P Prabitha; S Dhivya; S Yuvaraj; Pradeep Kabadi; Satheesh John Sekhar; C H Sandhya; Ashish D Wadhwani; Selvaraj Divakar; Jeyabalan Jeyaram Bharathi; Priya Durai; B R Prashantha Kumar Journal: Neurotox Res Date: 2019-11-28 Impact factor: 3.911