Abstract
Previously, we reported the successful regeneration of injured peripheral nerves using human dental pulp stem cells (DPSCs) or differentiated neuronal cells from DPSCs (DF-DPSCs) in a rat model. Here, we attempted to evaluate oxidative stress and supraspinal neuro-inflammation in rat brain after sciatic nerve injury (SNI). We divided our experimental animals into three SNI groups based on time. The expression of a microglial (Iba1) marker and reactive oxygen species (ROS) was lower in DPSCs and higher in DF-DPSCs. In contrast, the expression of an astroglial (GFAP) marker was higher in DPSCs and lower in DF-DPSCs at 2 weeks. However, the expression of ROS, Iba1 and GFAP gradually decreased at 8 and 12 weeks in the SNI DPSCs and DF-DPSCs groups compared to the SNI control. Furthermore, anti-inflammatory cytokine (IL-4 and TGF-β) expression was lower at 2 weeks, while it gradually increased at 8 and 12 weeks after surgery in the SNI DPSCs and DF-DPSCs groups. Similarly, SNI DPSCs had a high expression of pAMPK, SIRT1 and NFkB at the onset of SNI. However, 12 weeks after surgery, pAMPK and SIRT1 expression levels were higher and NFkB was down-regulated in both DPSCs and DF-DPSCs compared to the control group. Finally, we concluded that DPSCs responded early and more efficiently than DF-DPSCs to counterbalance peripheral nerve injury (PNI)-induced oxidative stress and supraspinal neuro-inflammation in rat brain.
Highlights
Mesenchymal stem cells (MSCs) are considered one of the most important cell types for regenerative medicines
After 2 weeks, we found low expression of Iba[1] and high expression of GFAP in sciatic nerve injury (SNI) dental pulp stem cells (DPSCs) compared to other groups, while SNI DF-DPSCs had inverse results (Fig. 1Aa,Ba)
After 12 weeks, both DPSC groups had significantly low expression of Iba[1] and GFAP compared to controls, though DF-DPSCs had the lowest expression among the three groups (Fig. 1Ac,Bc)
Summary
Mesenchymal stem cells (MSCs) are considered one of the most important cell types for regenerative medicines. Peripheral neuropathy induces the release of inflammatory mediators within the brain, but surprisingly little attention has been paid to this supraspinal neuro-inflammation[14]. Neuropathic pain causes anxiety and depressive-like behavior in patients as well as neuropsychiatric disorders, which are associated with the release of pro-inflammatory cytokines and chemokines[15,16,17]. Patients suffering from affective disturbances, i.e., depression and stress, have a strong inflammatory component with higher levels of blood pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor (TNF)[18,19]. We evaluated the relieving effect of dental pulp stem cells (DPSCs) and neuronal differentiated DPSCs (DF-DPSCs) on peripheral nerve injury-induced neuro-inflammation in the brain of a sciatic nerve injury (SNI) rat model
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