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Small-molecule agonists of TrkB (e.g., 7,8-dihydroxyflavone) can penetrate the blood-brain barrier and potentially activate BDNF signaling while supporting mitochondrial function [120], but their specificity and long-term safety in humans remain questionable, and they do not address the fundamental barrier of blood-brain barrier penetration for large-molecule NTFs (e.g., GDNF)

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These mechanisms include changes in microbial composition, immune activation, vagus nerve signaling, and the production of specific microbial neuroactive metabolites (197)

Clinical use: Supervised protocols at medical clinics involve subcutaneous injection over 4 to 8 weeks, with dosing individualized to injury type and severity