Noradrenaline-mediated protection against TNF-alpha-induced neuronal atrophy

Abstract

injury (SCI) in rodent. However, it is still unclear that the PACAP induced by hMSCs contributes to the cellar protection. Therefore, we examined effect of hMSCs on SCI of PACAP gene deficient mice. We also determined that hMSCs partially suppressed neural inflammation through PACAP with host tissues. Under inhalation of anesthesia, mice either PACAP+/+ (wild) or +/− (KO) were subjected to spinal cord transection by a razor at level of Th9–10 intervertebral spinal cord. One day later, the mice were injected hMSCs (5 × 10 cells/0.5 μL) or vehicle one caudal the intervertebral spinal cord. The mice were scored locomotor activity detected by Basso Mouse Scale (BMS) and evaluated injury area with glial fibrillary acidic protein (GFAP) surrounded area at 7 days post operation. We also examined mouse PACAP and PACAP specific receptor (PAC1R) and human or mice proand anti-inflammatory cytokine gene expressions. WTmice implanted hMSCs into spinal cord ameliorated significantly locomotor activity and injury volume to compare with vehicle-treated one. The protections were canceled by inviable hMSCs implanted into WT mice and by viable hMSCs implanted into KO mice. Spinal cord implanted hMSCs expressed an increase of mouse PACAP gene, but not PAC1R. The hMSCs implanted WT animals were decreased mouse IL-1, TNF-alpha, IL-10 and TGF-beta, and increased IL-4 compared with vehicle treatedWT one. However, given hMSCs into KOmice, IL-1, TGFbeta and IL-4 expressed similar to vehicle-treatedWT one. These results suggest that hMSCs suppress neural damage partially mediated by PACAP of mice and decrease of IL-1 and TGF-beta and increase of IL-4 were regulated by the PACAP expression.