Hyperforin promotes post-stroke functional recovery through interleukin (IL)-17A-mediated angiogenesis

Area of Science:

• Neuroscience
• Pharmacology
• Immunology

Background:

• Hyperforin, from Hypericum perforatum, shows neuroprotection in acute ischemic stroke.
• Long-term effects of hyperforin on post-stroke functional recovery and mechanisms remain unclear.

Purpose of the Study:

• Investigate the long-term effects of delayed hyperforin treatment on functional recovery after ischemic stroke.
• Elucidate the underlying mechanisms involving Interleukin-17A (IL-17A) and vascular endothelial growth factor (VEGF) signaling.

Main Methods:

• Middle cerebral artery occlusion (60min) followed by 28 days of reperfusion in C57BL/6 wild-type and IL-17A knock-out mice.
• Delayed administration of hyperforin, anti-IL-17A monoclonal antibody (mAb), or recombinant mouse IL-17A (rIL-17A).
• Assessment of functional recovery and measurement of IL-17A, VEGF, and CD34 expression in the ischemic hemisphere.

Main Results:

• Delayed hyperforin treatment significantly improved functional recovery and increased IL-17A expression at 28 days post-ischemia.
• IL-17A deficiency or blockade attenuated hyperforin's beneficial effects on functional recovery.
• IL-17A signaling promoted angiogenesis via VEGF and CD34 expression, contributing to functional recovery.

Conclusions:

• Hyperforin promotes functional recovery in later stroke phases, not just acute neuroprotection.
• The IL-17A/VEGF signaling pathway is crucial for hyperforin-mediated angiogenesis and functional recovery post-stroke.
• This study uncovers a novel role for IL-17A in hyperforin's long-term stroke recovery effects.