Electroacupuncture at the Auricular Concha Regulates the Hippocampal SIRT1/CREB/BDNF Axis and Promotes Neurogenesis in Rats with Post-Stroke Depression

Abstract

Background and Objectives: Post-stroke depression (PSD) arises frequently after cerebral ischemia and worsens functional outcome, yet its pharmacological management remains suboptimal. Auricular-concha electroacupuncture (EA) activates afferents of the auricular branch of the vagus nerve and shows antidepressant promise; however, its effect on hippocampal neurogenesis and the underlying signaling cascade is incompletely characterized. This study examined whether EA at the auricular concha relieves depressive-like behavior and neurological deficits in PSD rats by stimulating hippocampal neurogenesis through the SIRT1/CREB/BDNF pathway. Methods: Male Sprague–Dawley rats were allocated into Control, Sham, PSD, and PSD + EA groups (n = 10). PSD was induced by permanent middle cerebral artery occlusion combined with chronic unpredictable mild stress and single housing. EA (square wave, 0.5 mA, 10/25 Hz, 30 s on/2 min off, 1 h/day, 28 days) was applied to the left auricular concha. Body weight, neurological severity (mNSS), sucrose preference, open-field, and forced-swim tests were evaluated at 24 h, 14 d, and 28 d. Neuronal morphology (HE), cell proliferation (Ki67), and the progenitor marker Nestin were assessed, and SIRT1, CREB, and BDNF expression was quantified by RT-PCR and Western blot. Results: PSD rats displayed higher mNSS, reduced body weight, lower sucrose preference and locomotion, and prolonged immobility (all p < 0.05 vs. Control). EA reversed each abnormality at 14 d and 28 d (p < 0.05 vs. PSD). Histology revealed neuronal loss and disarray in CA1, CA3, and the dentate gyrus, together with fewer Ki67-positive cells and diminished Nestin immunoreactivity; EA attenuated these changes. At the molecular level, PSD reduced SIRT1, p-CREB, and BDNF expression, which EA partially restored (p < 0.05 vs. PSD). Conclusion: Auricular-concha EA mitigates depressive-like and neurological deficits in PSD rats, an effect linked to enhanced hippocampal neurogenesis and re-activation of the SIRT1/CREB/BDNF cascade, supporting further translational evaluation.