Mesenchymal Stem Cells Regulate Activation of Microglia Cells to Improve Hippocampal Nerve Damage of Heat Stroke Rats

Abstract

Background: Heat stroke (HS) is a severe systemic inflammatory response disease caused by high fever, mainly with nervous system damage. Currently, mesenchymal stem cells (MSCs) have inflammation and immunomodulatory effects. Therefore, we aimed to explore the protective effect and mechanism of MSCs on HS-induced excessive inflammation and neurological dysfunction.Methods: A heat stroke Sprague-Dawley (SD) rat model was established at continuous high temperature (42 °C) and high humidity (70%-80%). After modeling, the rats were randomly divided into a heat stroke model group (HS group), a MSCs treatment group (HS+MSCs group), and a Control group in which the rats were kept at room temperature without any treatment. Survival analysis, neurological deficit scoring, pathological staining of hippocampus and cerebellum, immunofluorescence staining of microglia cells, and tissue level detection of inflammatory cytokines were performed in the three groups on day 1, 3, 7, 14 and 28 separately.Results: After heat stroke modeling, the rats were severely paralyzed and had a high mortality. MSCs treatment significantly reduced the mortality in both early stage (day 3) and late stage (day 28). MSCs treatment also significantly reduced the neurological impairment of heat stroke rats, and improved hippocampal and cerebellar pathology and neuronal cell damage. In addition, MSCs treatment significantly inhibited the overactivation of microglia in the hippocampus of HS rats as well as the levels of pro-inflammatory factors and chemokines in the hippocampus. In the early stage (day 1) of MSCs treatment, the activation of cerebellar microglia in the heat stroke rats was significantly promoted. Meanwhile, MSCs treatment had no significant inhibitory effect on the levels of pro-inflammatory factors in the cerebellar tissues of heat stroke rats, but can inhibit the levels of chemokines in the early stage.Conclusions: The application of MSCs for heat stroke treatment in rats can significantly reduce the mortality and neurological defects and improve the hippocampal injury. Meanwhile, MSCs can inhibit the over-activation of microglia cells in the hippocampus of heat stroke rats, which may be a mechanism of MSCs in protecting heat-stroke-caused hippocampal injury.