Cardio-Cerebral Protection by Electroacupuncture in a Murine Model of Chronic Hypoxia

Summary

This study established a 12-week chronic hypoxia murine model to investigate the cardio-cerebral protection of electroacupuncture. The findings demonstrated that electroacupuncture stimulation at acupoints commonly used to improve cognitive function not only enhanced cognitive function but also alleviated cardiac dysfunction and reduced pathological damage in myocardial tissue.

Abstract

This study established a 12-week chronic hypoxia murine model to investigate the cardio-cerebral protective effects of electroacupuncture. Existing therapeutic approaches for hypoxia-related disorders, such as hyperbaric oxygen therapy and certain pharmaceuticals, are frequently constrained by poor accessibility or single-target mechanisms. To address this gap, we hypothesized that EA stimulation at acupoints traditionally employed for cognitive enhancement could simultaneously improve both cognitive and cardiac functions under chronic hypoxic conditions. Thirty male C57BL/6J mice were randomly assigned to three groups: control group (Con), chronic hypoxia model group (CH), and chronic hypoxia plus electroacupuncture treatment group (CH+EA). The CH and CH+EA groups were exposed to a hypoxic environment (10.0% ± 0.5% O₂) for 8 h daily over 12 weeks, with the CH+EA group additionally undergoing daily EA stimulation at GV20, GV24, and bilateral ST36 during the last 2 weeks. Behavioral tests, echocardiographic assessment, and histopathological analysis revealed that EA not only significantly alleviated anxiety-like behaviors and improved spatial memory but also enhanced multiple cardiac function parameters, while reducing hippocampal neuronal damage and myocardial remodeling. These findings demonstrate that EA confers cardio-cerebral protective effects, which align with the Traditional Chinese Medicine "holistic concept", thereby providing a novel non-pharmacological intervention strategy for hypoxia-related cardiocerebral comorbidities.

Introduction

Hypoxia represents a common pathological challenge in various conditions, including high-altitude environments, chronic obstructive pulmonary disease (COPD), cardiocerebrovascular diseases, as well as specialized scenarios such as aerospace and diving operations, potentially leading to multi-organ functional impairment. As the organs with the highest oxygen consumption in the body, the brain and heart are particularly vulnerable to hypoxic damage. Studies demonstrate that the prevalence of cognitive impairment in COPD patients ranges from 32% to 88%^1,2, while the incidence of cardiac dysfunction reaches up to ....

Protocol

Thirty male C57BL/6J mice, aged 7-8 weeks and weighing 18-22 g (see Table of Materials), were housed in a SPF facility at the New Drug Evaluation Center of Hebei Yiling Pharmaceutical Research Institute. The ambient temperature was maintained at 20-26 °C with a relative humidity of 40%-70%, under a 12/12-h light/dark cycle. The mice had ad libitum access to standard laboratory rodent chow and clean water. After a 1-week acclimatization period, the mice were randomly allocated into three groups (n = 10): the normal control group (Con), the chronic hypoxia model group (CH), and the chronic hypoxia plus electroacupuncture treatment group (CH+EA). Al....

Results

Electroacupuncture ameliorates anxiety-like behavior and cognitive dysfunction induced by chronic sustained hypoxia in mice.

Anxiety-like behavior in mice subjected to CH was first assessed using OFT (Figure 3A). Trajectory plots revealed distinct behavioral patterns: control mice exhibited robust exploratory tendencies in the novel environment, with movement patterns covering the entire arena while predominantly concentrating in the corner zones .......

Discussion

This study confirms that long-term chronic hypoxia can induce anxiety-like behaviors and spatial memory impairment in mice, which is consistent with previous research findings^26,27. Meanwhile, we found that long-term chronic hypoxia can also cause cardiac dysfunction and myocardial structural damage. However, there is currently a lack of therapeutic strategies that can simultaneously ameliorate hypoxia-induced cognitive and cardiac impairments. To this end, we ev.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
10% paraformaldehyde solution	Bioroyee (Beijing) Biotechnology Co., Ltd	RL3234
ANY-maze	Science	SA201	Video tracking system
C75BL/6J mice	BEIJING HFK BIOSCIENCE CO.,LTD	No.110322220103041767	Gender: Male,  Weight: 18–22 g
Disposable acupuncture needles	Huatuo	246076	Sterile acupuncture needles for single use (0.25 mm ´ 13 mm)
Electroacupuncture device	Great Wall	KWD-808 I
HistoCore MULTICUT - Semi-Automated Rotary Microtome	Germany, Leica	RM2245	Paraffin slicer
Hwato acupuncture  needle	Suzhou Medical Appliance Factory	2655519
Isoflurane	RWD Life Science Co.,Ltd	R510-22
Masson’s Trichrome Stain Kit	solarbio	G1340	Masson staining kit
Morris water maze	Sansbio	SA201	Morris water maze device
NanoZoomer Digital Pathology	Hamamatsu Photonics K. K	C9600-01
NDP. View 2	Japan, Sakura		Slide scanner software
Small animal anesthesia machine	RWD	YL-LE-A106
Tissue Tech Prisma Plus	Japan, Sakura	20B2X00014000034	Fully automated device designed for staining specimens such as paraffin-embedded tissue sections, frozen sections, and slide-mounted cells.
Tissue-Tek TEC 6 Embedding Module	Japan, Sakura	M01-021E-02	Paraffin embedding machine