Figure 3.

The potential central regulatory mechanism of acupuncture for PI. (1) Acupuncture improves brain function by regulating brain regions such as the default network and frontal lobe network. (2) Acupuncture improves the sleep–wake cycle by increasing the expression of neurotransmitters such as 5-HT, MT and GABA and reducing the expression of DA NE, and Glu and the Glu/GABA ratio. (3) Acupuncture affects sleep rhythm by regulating the expression of circadian clock genes, specifically by upregulating the clock, Bmal1, and Per genes. () The therapeutic effects of acupuncture in relieving brain tissue damage involve the promotion of inflammatory factor synthesis and modulation of neurotransmitter release. (5) Acupuncture influences energy metabolism by regulating AMPK-related pathways. (6) The neuroprotective effects of acupuncture are attributed to its ability to inhibit neuronal apoptosis through the regulation of the PI3K/AKT, PKA/CREB or BDNF/TrkB signaling pathway, thereby restoring nerve function. MA, manual acupuncture; EA, electroacupuncture; taVNS, transcutaneous auricular vagus nerve stimulation; SA, superficial acupuncture; 5-HT, 5-hydroxytryptamine; NE, noradrenaline; DA, dopamine; MT, melatonin; Glu, glutamic acid; GABA, γ-aminobutyric acid; Per1, period1; Bmal1, bain and muscle arnt-like protein-1; Clock, circadian locomotor output cycles kaput; TNF-α, tumour necrosis factor alpha; IL-1β, interleukin-1beta; AMPK, adenosine 5′-monophosphate (AMP)-activated protein kinase; Ac-CoA, acetyl-coenzyme A; ATP, adenosine triphosphate; TrkB, tropomysin related kinase B; PI3K, phosphoinositide 3-kinase; Akt, protein kinase B; PKA-Cβ, catalytic subunit of protein kinase A; p-CREB, phosphorylated cAMP-responsive element-binding protein; BDNF, brain-derived neurotrophic factor.