Hydrogen Gas Shows Gender Differences in Treating Post-Stroke Depression
- Authors
- Ping An, Xiao-Chun Zhao, Man-Jia Liu, Yu-Qing You, Jing-Ya Li
- Journal
- Neurochemistry International
- Year
- 2022
- DOI
- 10.1016/j.neuint.2022.105276
- Study Type
- Mouse
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- China
- Health Condition
- Post-Stroke Depression
- Body System
- Nervous System
TL;DR
Estrogen appears to enhance the brain-protective effects of hydrogen gas treatment in male mice recovering from a type of stroke that causes brain bleeding and depression.
Key Finding
Estrogen enhanced the neuroprotective effects of hydrogen gas in male mice with brain hemorrhage-induced depression, while female mice showed greater baseline sensitivity to hydrogen gas treatment.
Summary
This mouse study investigated whether hydrogen gas could help reduce depression-like symptoms after a type of brain bleeding called intracerebral hemorrhage. Researchers found that hydrogen gas worked better in female mice naturally, but when they gave male mice estrogen (a hormone), it made hydrogen gas work much better in them too. The improvement appeared to involve reducing brain inflammation and harmful molecules called free radicals.
Practical Takeaway
This early-stage mouse study suggests that sex hormones may influence how effectively hydrogen gas protects the brain after certain types of injury, which could eventually inform personalized treatment approaches. However, this is animal research only, and it remains unclear whether these findings would apply to humans or how they might translate to clinical use.
Abstract
Background: Post-stroke depression (PSD) severely affects recovery in patients with intracerebral hemorrhage (ICH). Although hydrogen gas (H2) exerts excellent neuroprotective effects in patients with ICH, there are sex-based differences in H2 efficacy in several diseases. Herein, we determined whether estrogen increases susceptibility to the neuroprotective effects of H2 in males with ICH-induced depression. Methods: A rodent model of ICH in the basal ganglia was established using autologous blood injection (30 μL). Mice were treated with 2.9% H2 for 2 h daily for 3 days post-ICH. Estrogen (1 mg/kg) was administered by subcutaneous injection daily for 3 days to male mice post-ICH. Thirty days post-ICH, PSD was evaluated by sucrose preference, forced swimming, and 3-chamber social tests. Following the completion of behavioral tests, levels of superoxide dismutase (SOD) and reactive oxygen species (ROS), astrocytic activation, phosphorylated (p)-NF-κB-positive astrocytes, p-NF-κB, p-IKKβ, IL-1β, and IL-6 expression were determined. Results: Compared with female mice, H2 administration post-ICH exhibited fewer neuroprotective effects, including decreased sucrose consumption and time spent sniffing a novel mouse, increased immobility time, downregulated total SOD content, upregulated ROS content and p-NF-κB levels, and elevated astrocyte branches, whereas estrogen enhanced the neuroprotective effects of H2 in male mice. A reduced number of p-NF-κB-positive astrocytes, downregulated expression of p-NF-κB, p-IKKβ, IL-1β, and IL-6 in the amygdala were demonstrated in ICH-males treated with estrogen plus H2. Conclusions: Estrogen was responsible for increased H2 sensitivity in male mice with ICH. The underlying mechanism may be associated with the suppression of NF-κB signaling in astrocytes.