Appropriate supplementation of testosterone alleviates post-stroke damage via decreasing inflammation and oxidative stress in aged male C57BL/6 mice

Abstract

Stroke injury is closely related to testosterone levels. Testosterone supplementation in elderly men is seen to protect the cardiovascular system and reduce the risk of stroke. But this medication method is controversial. This study aims to investigate the effect of long-term testosterone supplementation on brain injury after stroke in aged mice. 60 male C57BL/6 mice,12-months of age were divided into 3 groups: low-dose group, high-dose group, and control group, each group was injected subcutaneously with 100 μL of sesame oil or 5 mg/kg or 50 mg/kg of testosterone (in 100 μL of sesame oil) twice per week, respectively. One week after the injection, stroke was induced by light. After the stroke, the injection continued for 6 weeks. The motion ability was measured by rotating rod and tail suspension. The brain injury was observed by naked eyes and TTC staining. In addition, we measured the inflammation ( Tnf-α, Il-6, and Mcp-1) and oxidative stress (Malondialdehyde (MDA) and T-AOC) in the injured tissue 72 h post-stroke. Low-dose testosterone supplementation improved the motion ability and decreased brain injury. It also decreased the inflammatory factors ( Tnf-α, Il-6, and Mcp-1), decreased MDA product, and increased T-AOC. High-dose testosterone supplementation not only reduced the motion ability and aggravated stroke injury, but also increased the inflammation, MDA level and decreased T-AOC level. In summary, supplementation of testosterone at normal levels in elderly mice can alleviate post-stroke injury by reducing inflammation and oxidative stress; however, excessive supplementation may cause unexpected injuries. This study has important implications for the application of testosterone replacement therapy.