Mesenchymal Stromal Cells Suppress Hippocampal Neuron Autophagy Stress Induced by Hypoxic-Ischemic Brain Damage: The Possible Role of Endogenous IL-6 Secretion.

Miao Yang,Mulan He,Lu Xiao,Ting Yang,Yan Gu,Wuqing Sun,Xiaohua Liang,Jie Chen,Fushun Wang

doi:10.1155/2020/8822579

Miao Yang, Mulan He + Show 7 more

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https://doi.org/10.1155/2020/8822579

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Abstract

Background Increasing evidence has revealed that mesenchymal stromal cell (MSC) transplantation alleviates hypoxic-ischemic brain damage (HIBD) induced neurological impairments via immunomodulating astrocyte antiapoptosis effects. However, it remains unclear whether MSCs regulate neuron autophagy following HIBD. Results In the present study, MSC transplantation effectively ameliorated learning-memory function and suppressed stress-induced hippocampal neuron autophagy in HIBD rats. Moreover, the suppressive effects of MSCs on autophagy were significantly weakened following endogenous IL-6 silencing in MSCs. Suppressing IL-6 expression also significantly increased p-AMPK protein expression and decreased p-mTOR protein expression in injured hippocampal neurons. Conclusion Endogenous IL-6 in MSCs may reduce autophagy in hippocampal neurons partly through the AMPK/mTOR pathway.

Highlights

Increasing evidence has revealed that mesenchymal stromal cell (MSC) transplantation alleviates hypoxic-ischemic brain damage (HIBD) induced neurological impairments via immunomodulating astrocyte antiapoptosis effects
The levels of p62 protein expression were significantly increased in the HIBD hippocampus at 12 h and 24 h after MSC transplantation (Figures 1(a) and 1(d))
The above results demonstrated that MSC transplantation may regulate the level of hippocampal autophagy

Summary

Introduction

Increasing evidence has revealed that mesenchymal stromal cell (MSC) transplantation alleviates hypoxic-ischemic brain damage (HIBD) induced neurological impairments via immunomodulating astrocyte antiapoptosis effects. It remains unclear whether MSCs regulate neuron autophagy following HIBD. MSC transplantation effectively ameliorated learning-memory function and suppressed stress-induced hippocampal neuron autophagy in HIBD rats. The suppressive effects of MSCs on autophagy were significantly weakened following endogenous IL-6 silencing in MSCs. Suppressing IL-6 expression significantly increased p-AMPK protein expression and decreased p-mTOR protein expression in injured hippocampal neurons. More and more studies have demonstrated the involvement of autophagy in cerebral ischemic stroke; it remains unclear what effects transplanted mesenchymal stromal cells (MSCs) have on autophagy following ischemic cerebral injury

Results

Discussion

Conclusion