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Second, human VNS relies more on the multi-pathway synergy after central integration (such as the cholinergic anti-inflammatory pathway), and does not only depend on the direct vagus nerve control, and the core mechanisms such as anti-inflammatory (inhibiting TNF-, IL-6), regulation of neurotransmitters (reducing 5-HT), and improvement of intestinal motility are consistent across species (3, 4, 19)

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Systemic injection of AAV9-GDNF provides modest functional improvements in the SOD1G93A ALS rat but has adverse side effects