Electroacupuncture alleviated post-stroke cognitive impairment via the mTOR/NLRP3-mediated autophagy-inflammatory pathway

Eur J Med Res. 2024 Nov 5;29(1):532. doi: 10.1186/s40001-024-02131-9.

Abstract

Background: Post-stroke cognitive impairment (PSCI) severely reduces quality of life of patients with stroke. This study aimed to assess the effects of electroacupuncture (EA) on PSCI and the role of the mTOR/NLRP3-mediated autophagy-inflammatory pathway in this process.

Methods: The rat focal cerebral ischemia model was established using middle cerebral artery occlusion (MCAO). Following successful induction of the model, EA was applied to the bilateral Fengchi, Fengfu, and Dazhui acupoints, and brain tissue samples were collected on day 15. Cognitive function was assessed using the Morris water maze test. Cerebral infarct volume was quantified by Triphenyltetrazolium chloride (TTC) staining. Hematoxylin-eosin and TUNEL staining were performed to evaluate pathological changes and apoptosis rates. Apoptosis-, inflammation-, and autophagy-related biomarkers were measured, and autophagosomes were visualized using transmission electron microscopy.

Results: MCAO rats exhibited slower weight gain, reduced mobility, increased infarct size, pathological damage, and apoptosis, confirming successful establishment of the MCAO rat model. Following EA treatment, MCAO rats displayed faster weight gain, improved mobility, and shorter escape latency. EA also reduced the area of cerebral infarction and alleviated pathological damage and apoptosis in MCAO rats. Furthermore, EA downregulated IL-1β, IL-18, NLRP3, and LC3 II/LC3 I expression and upregulated p62, mTOR, and Beclin-1 expression in MCAO rats. EA treatment also decreased the number of autophagosomes in these rats.

Conclusions: EA effectively mitigates post-stroke cognitive impairment by reducing apoptosis, inflammation, and autophagy through the regulation of the mTOR/NLRP3-mediated autophagy-inflammatory pathway, offering valuable therapeutic insights for stroke rehabilitation.

Keywords: Apoptosis; Autophagy; Inflammation; Post-stroke cognitive impairment; mTOR/NLRP3 pathway.

MeSH terms

  • Animals
  • Apoptosis
  • Autophagy*
  • Cognitive Dysfunction* / etiology
  • Cognitive Dysfunction* / metabolism
  • Cognitive Dysfunction* / therapy
  • Disease Models, Animal
  • Electroacupuncture* / methods
  • Infarction, Middle Cerebral Artery / complications
  • Infarction, Middle Cerebral Artery / metabolism
  • Infarction, Middle Cerebral Artery / therapy
  • Inflammation / metabolism
  • Inflammation / therapy
  • Male
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
  • Rats
  • Rats, Sprague-Dawley*
  • Signal Transduction
  • Stroke / complications
  • Stroke / metabolism
  • TOR Serine-Threonine Kinases* / metabolism

Substances

  • NLR Family, Pyrin Domain-Containing 3 Protein
  • TOR Serine-Threonine Kinases
  • Nlrp3 protein, rat
  • mTOR protein, rat