Schwann cells are not only myelinating cells, but also function as immune cells and express numerous innate pattern recognition receptors, including the Toll-like receptors. Injury to peripheral nerves activates an in...Schwann cells are not only myelinating cells, but also function as immune cells and express numerous innate pattern recognition receptors, including the Toll-like receptors. Injury to peripheral nerves activates an inflammatory response in Schwann cells. However, it is unclear whether specific endogenous damage-associated molecular pattern molecules are involved in the inflammatory response following nerve injury. In the present study, we demonstrate that a key damage-associated molecular pattern molecule, high mobility group box 1（HMGB1）, is upregulated following rat sciatic nerve axotomy, and we show colocalization of the protein with Schwann cells. HMGB1 alone could not enhance expression of Toll-like receptors or the receptor for advanced glycation end products（RAGE）, but was able to facilitate migration of Schwann cells. When Schwann cells were treated with HMGB1 together with lipopolysaccharide, the expression levels of Toll-like receptors and RAGE, as well as inflammatory cytokines were upregulated. Our novel findings demonstrate that the HMGB1 pathway activates the inflammatory response in Schwann cells following peripheral nerve injury.展开更多
The management of traumatic peripheral nerve injury remains a considerable concern for clinicians.With minimal innovations in surgical technique and a limited number of specialists trained to treat peripheral nerve in...The management of traumatic peripheral nerve injury remains a considerable concern for clinicians.With minimal innovations in surgical technique and a limited number of specialists trained to treat peripheral nerve injury,outcomes of surgical intervention have been unpredictable.The inability to manipulate the pathophysiology of nerve injury（i.e.,Wallerian degeneration） has left scientists and clinicians depending on the slow and lengthy process of axonal regeneration（-1 mm/day）.When axons are severed,the endings undergo calcium-mediated plasmalemmal sealing,which limits the ability of the axon to be primarily repaired.Polythethylene glycol（PEG） in combination with a bioengineered process overcomes the inability to fuse axons.The mechanism for PEG axonal fusion is not clearly understood,but multiple studies have shown that a providing a calcium-free environment is essential to the process known as PEG fusion.The proposed mechanism is PEG-induced lipid bilayer fusion by removing the hydration barrier surrounding the axolemma and reducing the activation energy required for membrane fusion to occur.This review highlights PEG fusion,its past and current studies,and future directions in PEG fusion.展开更多
基金supported by the National Natural Science Foundation of China,No.31471011a grant from the National Program on Key Basic Research Project of China(973 Program),No.2014CB542202+1 种基金the Natural Science Foundation of Jiangsu Province of China,No.BK20131203a grant from the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)of China
文摘Schwann cells are not only myelinating cells, but also function as immune cells and express numerous innate pattern recognition receptors, including the Toll-like receptors. Injury to peripheral nerves activates an inflammatory response in Schwann cells. However, it is unclear whether specific endogenous damage-associated molecular pattern molecules are involved in the inflammatory response following nerve injury. In the present study, we demonstrate that a key damage-associated molecular pattern molecule, high mobility group box 1（HMGB1）, is upregulated following rat sciatic nerve axotomy, and we show colocalization of the protein with Schwann cells. HMGB1 alone could not enhance expression of Toll-like receptors or the receptor for advanced glycation end products（RAGE）, but was able to facilitate migration of Schwann cells. When Schwann cells were treated with HMGB1 together with lipopolysaccharide, the expression levels of Toll-like receptors and RAGE, as well as inflammatory cytokines were upregulated. Our novel findings demonstrate that the HMGB1 pathway activates the inflammatory response in Schwann cells following peripheral nerve injury.
基金supported by the Department of Defense:Grant Number OR120216--Development of Class Ⅱ Medical Device for Clinical Translation of a Novel PEG Fusion Method for Immediate Physiological Recovery after Peripheral Nerve Injury
文摘The management of traumatic peripheral nerve injury remains a considerable concern for clinicians.With minimal innovations in surgical technique and a limited number of specialists trained to treat peripheral nerve injury,outcomes of surgical intervention have been unpredictable.The inability to manipulate the pathophysiology of nerve injury（i.e.,Wallerian degeneration） has left scientists and clinicians depending on the slow and lengthy process of axonal regeneration（-1 mm/day）.When axons are severed,the endings undergo calcium-mediated plasmalemmal sealing,which limits the ability of the axon to be primarily repaired.Polythethylene glycol（PEG） in combination with a bioengineered process overcomes the inability to fuse axons.The mechanism for PEG axonal fusion is not clearly understood,but multiple studies have shown that a providing a calcium-free environment is essential to the process known as PEG fusion.The proposed mechanism is PEG-induced lipid bilayer fusion by removing the hydration barrier surrounding the axolemma and reducing the activation energy required for membrane fusion to occur.This review highlights PEG fusion,its past and current studies,and future directions in PEG fusion.
