Two faces of chondroitin sulfate proteoglycan in spinal cord repair: A role in microglia/macrophage activation (Plos Medicine, 2008, 5(8); e171:1262-1277)

報告日期: 2008/12/30
報告時間: 15:10/16:00
報告學生: 楊正昌
講評老師: 張權發

Two Faces of Chondroitin Sulfate Proteoglycan in Spinal Cord Repair: A Role in Microglia/Macrophage Activation

PLoS Medicine 5, 1262-1277 (2008)


Speaker: Cheng-Chang Yang

Commentator: Chuan-Fa Chang Ph. D.

Date: 12-30-2008

Time: 15:10- 16:00

Place: Room No. 602



Individual paralyzed was the most common pathological condition after spinal cord trauma in human. The pathophysiological mechanisms of spinal cord injury (SCI) were much clear in past three decade, basically included acute, subacute and chronic stage through the time progressing. SCI resulted in ischemia and hypoxia followed by a series degeneration event, including inflammation, ion unbalance, glutamate releasing and demyelination. Previously studies showed that the principal environmental feature of the damaged CNS is the glial scar. The chondroitin sulfate proteoglycan (CSPG) was the major constitute of this tough tissue, acts as a physical and biochemical barrier to axon regeneration. Degradation of this component lead to axonal reconnection was an artifice therapy in abundant studies. In this study, authors expected to investigate the role of CSPG in regulated microglia/macrophage activation and the beneficial during the repair progressing. The adult C57Bl/6J mice were employed SCI to examine the role of CSPG during recovery. Administration of xyloside, a kind of CSPG biosynthesis inhibitor, in different time point after spinal cord injury was used to analyze the phenotype of microglia/macrophagy. To tell resident microglia from infiltrated monocyte, they used chimeric mice whose monocyte expressed GFP.  They found CSPG inhibition right after SCI increased tissue loss, elevated the TNF-αexpression, level down the functional recovery and decreased IGF-1 expression. Furthermore, immediate inhibition of CSPG caused GFP-labeled monocyte infiltrated into epicenter. In contrast, delayed treatment, 2 days after SCI, of xyloside improved the function recovery. In vivo studies showed CSPG activated microglia/macrophage via CD44 receptor. Their results suggest that CSPG play a critical role to promote motor function recovery after spinal cord injury during the acute stage but not chronic stage.   



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