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High molecular weight form of hyaluronic acid reduces neuroinflammatory response in injured sciatic nerve via the intracellular domain of CD44
Author(s) -
Jou IMing,
Wu TungTai,
Hsu CheChia,
Yang ChengChang,
Huang JhyShrian,
Tu YuanKun,
Lee JungShun,
Su FongChin,
Kuo YaoLung
Publication year - 2021
Publication title -
journal of biomedical materials research part b: applied biomaterials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.665
H-Index - 108
eISSN - 1552-4981
pISSN - 1552-4973
DOI - 10.1002/jbm.b.34731
Subject(s) - sciatic nerve , peripheral nerve injury , hyaluronic acid , proinflammatory cytokine , compound muscle action potential , sciatic nerve injury , tlr4 , chemistry , cd44 , pharmacology , nerve injury , crush injury , medicine , receptor , anesthesia , cell , inflammation , biochemistry , anatomy , electrophysiology , surgery
Inflammatory response after peripheral nerve injury is required for clearance of tissue debris and effective regeneration. Studies have revealed that hyaluronic acid (HA) may exert different properties depending on their molecular size. High molecular weight HA ( > >1,000 kDa; HMW‐HA) displays immunosuppressive properties, whereas low molecular weight HA (<800 kDa; LMW‐HA) induces proinflammatory responses. The role of HMW‐HA interaction with CD44, a major HA receptor, in neuroinflammatory responses has not been fully elucidated. The purpose of this experimental study was to investigate the effects of topical applications of HMW‐HA on the sciatic nerve injury in an adult rat model. At the crush site on the sciatic nerve, the recordings of compound muscle action potential (CMAP) and the levels of several proteins related to inflammatory response were assessed at time intervals of 2, 4, and 6 weeks postsurgery. Here, we show that the recovery effect of HMW‐HA treatment had significantly shortened latency and increased amplitude of CMAP compared with crushed alone, crushed plus γ‐secretase inhibitor with or without HA treatment at 6 weeks after surgery. Our data reveal that HMW‐HA could downregulate the expression of IL1‐β, TLR4, and MMP‐9, whereas these proteins expression were increased when the CD44‐ICD activity was inhibited using γ‐secretase inhibitor. Our findings demonstrated a novel role of CD44‐ICD in HA‐mediated recovery of peripheral nerve injury. Clinical relevance: an alternative for the regeneration of peripheral nerve injury.