21: LIPUS ameliorates perioperative neurocognitive disorder by inhibiting mitochondrial fission

Topic: Basic Science
Subtopic: Non-specific to any diagnosis (including studies in healthy animals), Non-pharmacological interventions

Background and Aims: Low-intensity pulsed ultrasound (LIPUS) is a non-invasive brain stimulation technique that utilizes the biophysical effects of ultrasound to treat brain disorders and injuries. This study investigated whether hippocampal-targeted LIPUS could improve perioperative neurocognitive disorder (PND) in aged mice and explored its potential mechanisms.

Methods: 18-month-old C57BL/6 mouse model of PND was established via laparotomy and prolonged anesthesia. Mice received daily hippocampal-targeted LIPUS stimulation for 20 minutes over three consecutive days. Cognitive function, hippocampal mitochondrial ultrastructure, oxidative stress and synaptic markers were evaluated. Additionally, Mdivi-1 was administered to inhibit Drp1 in PND mice, and rAAV-hSyn-Dnm1l-EGFP was injected into the hippocampus of 2-month-old male mice to overexpress Drp1, followed with LIPUS treatment, to assess the role of Drp1 in LIPUS-mediated effects.

Results: Both LIPUS treatment and Drp1 inhibition effectively enhanced cognitive performance, ameliorated mitochondrial structural impairments, attenuated oxidative stress, and restored synaptic integrity in PND mice. Furthermore, LIPUS intervention reversed the aberrant upregulation of Piezo1 in PND model mice. Notably, in young adult mice with Drp1 overexpression, LIPUS similarly alleviated cognitive deficits, reversed the elevation of oxidative stress and synaptic loss, and inhibited excessive mitochondrial fission.

Conclusions: LIPUS can precisely and non-invasively target the hippocampus in aged mice. By effecting on the mechanosensitive Piezo1 channel and suppressing Drp1 expression in hippocampal mitochondria, LIPUS significantly attenuates mitochondrial fission, thereby reducing oxidative stress and improving cognitive function in a PND model.

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Presenting Author: Changqi Chen
Submitting Author: Changqi Chen

Senior Author: Jianhui Liu

IASP 2026 Global Year theme of Neuropathic Pain: No

• Xuanran Feng - Tongji Hospital Affiliated to Tongji University School of Medicine
• Xue Du - Tongji Hospital Affiliated to Tongji University School of Medicine
• Xueli Peng - Tongji Hospital Affiliated to Tongji University School of Medicine
• Yuanyuan Zuo - Tongji University School of Medicine
• Qihui wu - Shanghai Fourth People’s Hospital Affiliated to Tongji University School of Medicine
• Hang Song - Shanghai Jiao Tong University
• Junfeng Sun - Shanghai Jiao Tong University