Basic and clinical research on acupuncture for post-stroke depression: A narrative review

Table 1 Mechanistic advances in acupuncture for post-stroke depression

Mechanism category	Specific regulatory targets	Pathological mechanism of PSD	Mechanism of acupuncture action	Ref.
Neurotransmitter regulation	Monoamine neurotransmitters (5-HT, NE, DA)	Brain injury reduces the synthesis of monoamine neurotransmitters, which is negatively correlated with the severity of depression	Promotes tryptophan transport and 5-HT synthesis, increases levels of 5-HT, NE, and DA in the brain, and repairs nerve conduction pathways	[10-14]
	Amino acid neurotransmitters (Glu, GABA)	Brain injury leads to Glu accumulation (neurotoxicity) and GABA imbalance, inducing depression	Downregulates Glu and GABA contents in the hippocampus and caudate putamen, reducing Glu-mediated nerve damage	[15-19]
Neurotrophic factor regulation	BDNF and its receptor TrkB	Post-stroke reduction in BDNF levels inhibits the regeneration of 5-HT neurons, leading to decreased neural excitability	Activates the BDNF-TrkB signaling pathway, increases peripheral blood BDNF content, and promotes the recovery of hippocampal neuron function	[20-24]
Neuroendocrine regulation	HPA axis and CRH, ACTH, CORT	HPA axis hyperfunction increases CRH, ACTH, and CORT levels, which are positively correlated with depression and anxiety	Regulates monoamine neurotransmitters, affects hippocampal function and hypothalamic mRNA expression, reducing CRH, ACTH, and CORT levels	[13,25-29]
Inflammatory cytokine regulation	Proinflammatory cytokines (IL-2, IL-6, TNF-α) and p38 MAPK signaling pathway	Activation of the p38MAPK pathway leads to excessive release of proinflammatory factors, depleting 5-HT and inducing neurotoxicity and depression	Inhibits the activation of the p38MAPK pathway, reduces levels of IL-2, IL-6, and TNF-α, and alleviates neuroinflammation and edema	[30-32]
Oxidative stress regulation	Antioxidant enzymes (SOD, GSH) and oxidative products	Post-stroke imbalance in the oxidation-antioxidation system, reduced SOD and GSH, and accumulation of free radicals leading to neuronal apoptosis	Reduces levels of IL-6 and TNF-α, thereby increasing SOD and GSH contents and alleviating oxidative stress damage	[27,33-35]
Serum protein regulation	SF	High SF induces oxidative stress through iron ions, causing neuronal death and depression	Mobilizes anti-inflammatory and antioxidant effects, reduces SF content, and decreases oxidative damage to nerve cells	[35,36]
	S100B protein	High expression of S100B impairs hippocampal and 5-HT system function, exacerbating depression	Reduces serum S100B concentration, repairs nerve function, and improves depressive mood	[37-39]
Other regulatory mechanisms	Brain-gut axis	Intestinal flora disorder causes intestinal inflammation, disrupting 5-HT signal transduction and aggravating depression	Mediates the brain-gut axis pathway by regulating serum 5-HT levels, alleviating gastrointestinal symptoms	[32,40]
	Blood homocysteine (Hcy)	High Hcy induces depression through inflammation, oxidative stress, and neurotoxicity	Regulates Hcy content to affect neurotransmitter secretion, promotes BDNF expression, inhibits cytokine production, and reduces inflammatory reactions	[41,42]

5-HT: 5-hydroxytryptamine; ACTH: Adrenocorticotropic hormone; BDNF: Brain-derived neurotrophic factor; CRH: Corticotropin-releasing hormone; DA: Dopamine; GABA: Gamma-aminobutyric acid; GSH: Glutathione; Hcy: Homocysteine; HPA: Hypothalamic-pituitary-adrenal; IL: Interleukin; MAPK: Mitogen-activated protein kinase; NE: Norepinephrine; PSD: Post-stroke depression; SF: Serum ferritin; SOD: Superoxide dismutase; TNF-α: Tumor necrosis factor alpha.

Table 2 Comparative efficacy and advantages of acupuncture therapies for post-stroke depression

Modality	Primary clinical applications and efficacy	Key advantages
Pure acupuncture	Alleviates core depressive symptoms; improves neurological function and daily living activities	Foundation of TCM treatment; addresses both root (deficiency) and branch (excess) causes
Electroacupuncture	Improves mood, cognition, and cortical excitability; offers sustainable short-term results	Combines TCM with electrical neurostimulation for potent effects
Specialty acupuncture techniques
Scalp acupuncture	Targets emotional brain regions; effective for emotional regulation and neuronal recovery	Highly targeted based on neuroimaging; provides sustained stimulation to specific areas
Auricular acupuncture	Provides durable antidepressant effects; improves overall quality of life	Minimally invasive with high compliance; allows for prolonged stimulation (e.g., with beads)
Comprehensive therapies
Acupuncture + herbal medicine	Rapid improvement in neurofunction; addresses complex TCM patterns like phlegm-stasis	Synergistic multi-target approach (anti-inflammatory, neurotrophic, gut microbiome)
Acupuncture + moxibustion	Supports neurological recovery and improves cognitive function	Adds a warming and tonifying effect, ideal for deficiency patterns
Acupuncture + music therapy	Improves mood and sleep; reduces depressive and gastrointestinal symptoms	Holistic approach that integrates sensory stimulation to regulate emotion and physiology
Acupuncture + rehabilitation training	Improves psychological resilience, neurofunction, and long-term outcomes	Integrates physical neuromodulation with behavioral/cognitive training for comprehensive rehab

TCM: Traditional Chinese medicine.