Dehydroepiandrosterone attenuates microglial activation and exerts neuroprotective effect after subarachnoid hemorrhage

Abstract

Objective To investigate the regulatory effect of dehydroepiandrosterone (DHEA) on the microglial activation after subarachnoid hemorrhage (SAH) in vivo and in vitro. Methods C57BL/6 mice were used for in vivo experiments. A SAH model was induced by intravascular puncture. They were randomly divided into solvent group, model group, and DHEA pretreatment group. TUNEL staining was used to detect neuronal apoptosis level at 24 h after modeling. Iba-1/CD86 fluorescence double staining was used to detect the activation of microglia. Quantitative fluorescent polymerase chain reaction and Western blot analysis were used to detect the expression of inflammatory factors, including interleukin (IL) -1β, IL-6, tumor necrosis factor (TNF) -α, and inducible nitric oxide synthase (iNOS). The primary cultured microglia was used for in vitro experiments and it was simulated SAH by hemoglobin stimulation. They were randomly divided into control group, model group, and DHEA pretreatment group. Iba-1/CD86 fluorescence double staining was used to detect the microglial activation, and fluorescence quantitative polymerase chain reaction and Western blot analysis were used to detect the expression of inflammatory factors. Results In vivo model experiments showed that DHEA significantly reduced neuronal apoptosis (P<0.01) and microglial activation (P<0.01) after SAH modeling, and IL-6 expression level significantly decreased (P<0.01), while IL-1β, TNF-α and iNOS showed a downward trend, but there were no statistical differences. In vitro model experiments showed that DHEA could significantly inhibit microglial activation (P<0.001) and the expression levels of various inflammatory factors (P<0.001). Conclusions DHEA pretreatment can reduce neuronal apoptosis and microglia activation after SAH, and it has neuroprotective effect. Key words: Subarachnoid haemorrhage; Microglia; Dehydroepiandrosterone; Inflammation; Neuroprotective agents; Disease models, animal; Mice