Title:Protective Effects of Mesenchymal Stem Cells Against Central Nervous
System Injury in Heat Stroke
Volume: 18
Issue: 3
Author(s): Rui Yuan, Lu Wang, Zi-Hui Deng, Meng-Meng Yang, Yan Zhao, Jie Hu, Yu Zhang, Yun Li, Meng Liu, Shi-Fei Liu, Fei-Hu Zhou, Hanyu-Zhu*Hong-Jun Kang*
Affiliation:
- State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing 100853, China
- Department of Critical Care Medicine, Chinese PLA General Hospital, Beijing 100853, China
- State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing 100853, China
Keywords:
Heat stroke, central nervous system, mesenchymal stem cells, brain-derived neurotrophic factor, P38 signal pathway, tumor necrosis factor.
Abstract:
Background: Heatstroke (HS) is a serious disease caused by central nervous system (CNS)
injuries, such as delirium, convulsion, and coma. Currently, mesenchymal stem cells (MSCs) have
demonstrated novel neuroprotective effects; therefore, this research explores the neuroprotective effects
and mechanisms of MSCs against HS injury.
Methods: HS rat models were induced in a 40°C and 65% humidity environment until the rectal temperature
reached 42°C. The verified HS injury model rats were divided into the HS and MSCs-treated groups.
Each rat in the treated group was infused with 1x106 MSCs suspended in 0.3 ml physiological saline via
the tail vein. The HS- or MSCs-treated rats were further divided into early-stage (3d) and late-stage (28d).
HS rat models were induced by a high-temperature and high-humidity environment at a specific time, the
mortality was analyzed, and an automatic biochemical analyzer measured levels of liver and kidney function
indicators in the blood. The neurons' morphologic changes were observed through Nissl staining, and
neurological deficit scores were performed. Moreover, the levels of inflammatory factors in brain tissue
were measured using a multi-cytokine detection platform, and the expression of BDNF, phosphorylated
TrkB and P38 were detected by the Western Bolt.
Results: MSCs injection significantly reduced mortality and alleviated liver and kidney function. Moreover,
the neurological deficit and neuronic edema of the hippocampus caused by HS at 3d and 28d were
significantly ameliorated by MSCs administration. Specifically, the injection of MSCs inhibited high
levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), and IL-17A caused by HS but elevated
the levels of IL-10 and IL-13 in the early period (3d); while in the later period (28d), MSCs significantly
increased the levels of IL-10 and IL-13 continuously and inhibited the high level of IL-17A. Furthermore,
MSCs injection increased the expressions of BDNF and phosphorylated TrkB (BDNF receptor),
meanwhile inhibiting the expression of phosphorylated P38 (inflammatory factor) in the brains of HS
rats in the early period (3d) but had no significant influence on the later period (28d).
Conclusion: These results suggested that MSCs injection may provide therapeutic effects for HS in rats
by improving liver and kidney function and reducing CNS damage. Moreover, MSCs injection inhibited
the brain inflammatory response of HS rats, and the BDNF-TrkB and P38/MAPK signal pathways may be
involved, providing a potential mechanism for HS therapy by MSCs administration.
