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Activation of peripheral TRPM8 mitigates ischemic stroke by topically applied menthol
Shiang-Suo Huang1,2,3, Hsing-Hui Su1,4, Szu-Yu Chien4
1Department of Pharmacology, Chung Shan Medical University, Taichung, 40201, Taiwan.
Journal of Neuroinflammation
|July 27, 2022
Summary
Topical menthol activates peripheral TRPM8 (transient receptor potential melastatin 8) receptors, reducing stroke damage and improving recovery. This approach, applied to limbs, shows promise as a novel stroke therapy.
Area of Science:
- Neuroscience
- Pharmacology
- Stroke Research
Background:
- Neuroprotective effects of topical TRPM8 activation are unexplored.
- Investigating TRPM8 activation as an adjuvant therapy for ischemic stroke.
Purpose of the Study:
- To determine if activating peripheral TRPM8 can serve as an adjuvant therapy for ischemic stroke.
Main Methods:
- Menthol (TRPM8 agonist) applied orally/topically to mice post-middle cerebral artery occlusion (MCAO).
- Utilized Trpm8 gene knockout mice, TRPM8 antagonist, and lidocaine to assess TRPM8 and nerve conduction roles.
- Compared topical menthol application on paws versus back.
Main Results:
- Topical 16% menthol on paws reduced infarct volumes and improved sensorimotor deficits in MCAO mice.
- Benefits linked to reduced oxidative stress, neuroinflammation, and immune cell infiltration in ischemic brains.
- Higher TRPM8 expression in paw skin correlated with greater neuroprotection compared to back application; nerve conduction blockade reversed effects.
Conclusions:
- Peripheral TRPM8 activation in limb skin with menthol aids stroke recovery.
- Topical menthol on hands/feet offers a novel, user-friendly therapeutic strategy for stroke patients.
