WITHDRAWN: Low-intensity pulsed ultrasound attenuates postoperative neurocognitive impairment and salvages hippocampal synaptogenesis in aged mice

Abstract

Background Postoperative neurocognitive impairment is an urgent problem with global aging accelerating. The prevention and treatment of postoperative neurocognitive impairment have been widely investigated but lack effective strategies. Low-intensity pulsed ultrasound (LIPUS), a non-invasive tool, has shown an effect on neuroprotection, but whether it could attenuate the postoperative neurocognitive impairment and the underlying mechanism remains unknow. Methods An experimental set-up for LIPUS stimulation of the hippocampus was well established. HE staining was used to determine the morphology of hippocampus after LIPUS application. A laparotomy model in aged mice was applied, and Morris water maze was used to assess cognitive function. RT-qPCR and western blotting were used to detect levels of inflammatory cytokines, synapse associated protein in the hippocampus, respectively. Immunofluorescent staining was also used to determine the neural activation and Piezo1 expression. Results After the anesthesia/surgery, the hippocampus of aged mice showed increased levels of inflammation and decreased synaptogenesis, while LIPUS intervention improved cognitive impairment, reduced hippocampal neuroinflammation, and improved synaptogenesis. We further found that LIPUS might improve synaptogenesis through the Piezo1-mediated calpain1/extracellular regulated protein kinases (Erk) pathway. Conclusion Our results suggested that LIPUS could be used as an effective physical intervention to improve postoperative cognitive dysfunction in the aged population.

Physical modulation of mesenchymal stem cell exosomes: A new perspective for regenerative medicine

“…Additionally, LIPUS has been acknowledged as a potent intervention to promote cartilage regeneration and osteogenic differentiation mediated by MSC‐Exo 31,42,126 . Besides, LIPUS could accelerate nerve injury repair 127,128 . Interestingly, MSC‐Exo also exhibit robust therapeutic potential in neurological diseases 129–131 .…”

“… 31 , 42 , 126 Besides, LIPUS could accelerate nerve injury repair. 127 , 128 Interestingly, MSC‐Exo also exhibit robust therapeutic potential in neurological diseases. 129 , 130 , 131 LIPUS has been confirmed as an effective intervention to augment the differentiation of neural stem cells into neural cells 132 and improve MSC‐based therapies for functional nerve recovery.…”