Calcitriol modulate post-ischemic TLR signaling pathway in ischemic stroke patients

Area of Science:

• Neuroscience
• Immunology
• Endocrinology

Background:

• Neuroinflammation significantly contributes to neuronal death post-stroke.
• Toll-Like Receptors (TLRs) are key mediators in inflammatory pathways, activating nuclear factor kappa β (NF-kβ) and promoting pro-inflammatory gene expression (e.g., IL-1β, IL-6).
• 1,25(OH)2D3 (calcitriol) is the active form of vitamin D3, possessing neurosteroid and anti-inflammatory properties.

Purpose of the Study:

• To investigate the modulatory effects of calcitriol on the post-ischemic immune response.
• To assess calcitriol's impact on the Toll-Like Receptor 4/nuclear factor kappa B (TLR4/NF-kB) signaling pathway in stroke patients.

Main Methods:

• Stroke was confirmed in 38 patients via neurological tests and blood markers.
• Gene expression of TLR4, TLR2, NF-kβ, IL-1β, and IL-6 was measured using real-time PCR.
• Protein expression of TLR4 and NF-kβ was assessed via flow cytometry; the experimental group received 10 μg of calcitriol orally.

Main Results:

• Ischemic stroke significantly increased the expression of TLR4, NF-kβ, IL-1β, and IL-6.
• Calcitriol demonstrated a modulatory effect on the TLR4/NF-kB signaling pathway within 24 hours post-ischemia.

Conclusions:

• Calcitriol may act as a protective agent following ischemia.
• By reducing TLR4/NF-kB activation, calcitriol may help mitigate stroke-related symptoms and improve patient outcomes.