Regulation Of Inflammation And Apoptosis After Spinal Cord Injury By Protocatechuic Aldehyde Via Wnt/β-catenin Signaling Pathway And Its Mechanism

Objective: This study aimed to explore the anti-inflammatory and neuroprotective effects of protocatechuic aldehyde(PCA)in rats with spinal cord injury(SCI)and to clarify the molecular mechanisms underlying its pharmacological effects.Methods: The Basso,Beattie,and Bresnahan scores and performance on the inclined plane test were evaluated.Histological analyses were performed via hematoxylin and eosin staining.Apoptosis in the spinal cord and neurons was detected by 5 terminal deoxynucleotidyl-transferase-mediated d UTP nick end labeling staining.Apoptotic factors(Bax,Bcl-2,and cleaved caspase-3)were also evaluated.INOS,IL-1β,IL-10,TNF-α,Wnt-3α,β-catenin,i BA-1,and Neu N were assessed by real-time reverse transcription-polymerase chain reaction(RT-PCR),western blotting(WB),and enzyme-linked immunosorbent assay.Cell viability and the immunofluorescence of IL-1β were measured in PC-12 cells.Results: Using WB and quantitative reverse transcription-PCR,we confirmed that PCA treatment activated the Wnt/β-catenin signaling axis in vivo and in vitro.Hematoxylin and eosin staining and hindlimb motor functional evaluation revealed that treatment with PCA improved tissue protection and functional recovery via the Wnt/β-catenin axis.The downregulation of TUNEL-positive cells,upregulation of neurons,elevated apoptosis-associated factors in rats,and decreased apoptotic rates were observed in microglia and PC-12 after PCA application.Finally,PCA mitigated SCI-induced inflammation by targeting the Wnt/β-catenin axis.Conclusion: This study provided preliminary evidence that PCA inhibits neuroinflammation and apoptosis through the Wnt/β-catenin pathway,thereby attenuating the secondary injury after SCI and promoting the regeneration of injured spinal tissues.