[Effect of Tongdu Tiaoshen acupuncture on hippocampal neuronal synaptic remodeling in rats with post-stroke depression based on the CCL2-CCR2 pathway].

PSD model rats exhibited significantly impaired hippocampal structure and synaptic integrity compared to blank controls.

• Model rats showed severe damage to hippocampal structure with reduced neuronal number and decreased synapse count and postsynaptic density
• Synaptic density (SD), postsynaptic density thickness (PSDL), and expression of SYN1, SYN, and PSD95 proteins were significantly decreased (P<0.05)
• Longa score, immobility time in forced swimming test, TNF-α and IL-6 levels were all increased (P<0.05)
• Sucrose preference index and IL-10 level were significantly decreased in model rats (P<0.05)

PSD model rats showed elevated expression of CCL2 and CCR2 proteins in the hippocampus compared to blank controls.

• CCL2 and CCR2 protein expression was significantly increased in model group compared to blank group (P<0.05)
• The model was established via middle cerebral artery occlusion (MCAO) combined with chronic unpredictable mild stress (CUMS)
• Western blot was used to detect CCL2-CCR2 pathway-related proteins
• 48 out of 50 rats were successfully modeled and used in the study

Tongdu Tiaoshen acupuncture improved hippocampal morphology and synaptic ultrastructure in PSD rats.

• Compared with the model group, the acupuncture group showed improved hippocampal structure with increased Nissl bodies and clearer neuronal nuclear membranes
• Synapse number and density increased, and postsynaptic density thickness increased in the acupuncture group (P<0.05)
• SD, PSDL, and SYN1, SYN, PSD95 protein expression were all significantly elevated compared to model group (P<0.05)
• Acupuncture was administered at GV14, GV26, GV24, and GV20, 40 min per session, once daily, 6 times per week

Tongdu Tiaoshen acupuncture reduced neurological deficit scores, depressive-like behavior, and pro-inflammatory cytokines in PSD rats.

• Longa score and immobility time in forced swimming test were significantly reduced in the acupuncture group compared to model group (P<0.05)
• Sucrose preference index was significantly increased in the acupuncture group compared to model group (P<0.05)
• TNF-α and IL-6 levels were decreased, while IL-10 level was increased in the acupuncture group (P<0.05)
• These improvements were comparable to those seen in the fluoxetine group (5 mg/kg by gavage)

Tongdu Tiaoshen acupuncture significantly downregulated CCL2 and CCR2 protein expression in PSD rats.

• CCL2 and CCR2 protein expression was significantly reduced in the acupuncture group compared to the model group (P<0.05)
• The fluoxetine group also showed reduced CCL2 and CCR2 expression compared to model group (P<0.05)
• Inhibition of the CCL2-CCR2 pathway is proposed as a mechanism by which acupuncture promotes hippocampal synaptic remodeling

Activation of the CCL2-CCR2 pathway via recombinant CCL2 protein partially reversed the beneficial effects of acupuncture.

• The acupuncture+agonist group received acupuncture combined with intraperitoneal injection of recombinant CCL2 protein (1 μg), once daily, 7 times per week
• Compared with the acupuncture+agonist group, the acupuncture group showed better improvement in all indexes (P<0.05)
• This finding supports a mechanistic role of the CCL2-CCR2 pathway in mediating acupuncture's effects on PSD

Both Tongdu Tiaoshen acupuncture and fluoxetine produced similar improvements across behavioral, inflammatory, and synaptic measures in PSD rats.

• Both groups showed reduced Longa score, immobility time, TNF-α, IL-6, CCL2, and CCR2 protein expression compared to model group (P<0.05)
• Both groups showed increased sucrose preference index, IL-10 level, SD, PSDL, and SYN1, SYN, PSD95 protein expression compared to model group (P<0.05)
• Fluoxetine dose was 5 mg/kg administered by gavage once daily, 7 times per week
• n=12 rats per group