Glucosamine-mediated immunomodulation after stroke is sexually dimorphic

Area of Science:

• Neuroscience
• Immunology
• Pharmacology

Background:

• Galectin-3 (Gal-3) plays a role in innate immune response and microglia activation in brain pathologies, but its precise function is debated.
• Glucosamine, a natural product and supplement for inflammatory conditions, has emerged as a potential modulator of Gal-3 signaling.
• Previous research suggests Gal-3 may be differentially regulated in female mice after ischemic injury.

Purpose of the Study:

• To investigate and compare the immunomodulatory effects of glucosamine in male and female mice following experimental stroke.
• To assess the impact of glucosamine on innate immune response, microglial activation, and lesion size in a sex-dependent manner.

Main Methods:

• Transient middle cerebral artery occlusion (MCAO) was performed on male and female mice.
• Glucosamine treatment (150 mg/kg i.p.) was initiated 2 hours after stroke and continued for 5 days.
• In vivo bioluminescence imaging using a TLR2-luc-GFP reporter system visualized innate immune response and microglial activation.
• Cytokine profiles and PPAR-γ activity were analyzed at the protein level post-stroke.

Main Results:

• Both male and female mice showed increased TLR2 bioluminescence after stroke, indicating innate immune activation.
• Glucosamine treatment in male mice reduced pro-inflammatory cytokines, increased anti-inflammatory cytokines (IL-4, IL13), and decreased ischemic lesion size.
• In contrast, glucosamine exacerbated inflammation and increased injury in female mice.
• Glucosamine restored PPAR-γ activity in males but not in females 3 days post-stroke.

Conclusions:

• Glucosamine exhibits sex-dependent immunomodulatory effects following ischemic stroke.
• Glucosamine demonstrates therapeutic potential in male stroke models by reducing inflammation and injury.
• Targeting the immune system after stroke may necessitate sex-specific therapeutic strategies.