Electroacupuncture therapy improves cognitive dysfunction after ischemic stroke in Sprague-Dawley rats by adjusting the lncRNA-MEG3/miR-4640-3p axis.

Abstract

Background: Ischemic stroke (IS) is a common disease that can cause cognitive dysfunction. Electroacupuncture (EA) is an effective way to alleviate cognitive dysfunction, but its molecular regulatory mechanism is still unclear. Long noncoding RNA-MEG3 (MEG3) is an important factor in the incidence and progression of IS. Herein, we explored the mechanism of EA in IS.

Methods: A middle cerebral artery occlusion (MCAO) model was established in Sprague-Dawley rats to simulate IS in vivo, followed by electroacupuncture (EA) therapy. AAV-control and AAV-MEG3 were injected into the lateral ventricle of rats. All rats except for the sham group underwent MCAO. EA was performed at Shenting and Baihui points for 30 min, once a day for 14 days. The MEG3 and miR-4640-3p levels in brains were measured by qRT-PCR. Dual-luciferase reporter analysis validated the relationship between MEG3 and miR-4640-3p. The Morris water maze test and the neurological function test were carried out. The pathological morphology of the brain tissue was evaluated by H&E staining. Apoptotic cells in brains were examined utilizing TUNEL staining. The contents of Bax, Bcl-2, caspase-3, and CytC were assessed by western blot.

Results: EA treatment reduced the content of MEG3 but enhanced miR-4640-3p levels in MCAO rats. MEG3 was a sponge for miR-4640-3p. EA treatment alleviated cognitive dysfunction in MCAO rats by inhibiting MEG3. EA treatment reduced MCAO-induced neural damage and apoptosis by inhibiting MEG3.

Conclusion: EA improved cognitive dysfunction in IS rats by adjusting the MEG3/miR-4640-3p axis, suggesting that EA may be an effective potential therapeutic strategy for improvement of cognitive dysfunction in IS. This study provided a more reliable experimental basis for clinical EA treatment of IS patients.