Transcranial near-infrared laser improves postoperative neurocognitive disorder in aged mice via SIRT3/AMPK/Nrf2 pathway

Abstract

BackgroundPostoperative neurocognitive disorder (PND) is a common central nervous system (CNS) complication that might increase the morbidity and mortality of elderly patients after anesthesia/surgery. Neuroinflammation, oxidative stress, and synaptic dysfunction are closely related to cognitive dysfunction, an important clinical feature of PND. Transcranial near-infrared laser (TNIL) is regarded as an effective treatment for cognitive-related diseases by improving mitochondrial function and alleviating neuroinflammation and oxidative stress damage.Materials and methodsAged male C57BL/6 mice underwent a carotid artery exposure procedure under isoflurane anesthesia. We treated PND-aged mice for three consecutive days (4 h post-operation, 1-laser) with 810 nm continuous wave (CW) laser 18 J/cm2 at 120 mW/cm2. The post-treatment evaluation included behavioral tests, RTq-PCR, immunofluorescence, and Western blot.ResultsThe results demonstrated that TNIL improved PND and the levels of synaptic function-associated proteins such as post-synaptic density protein 95 (PSD95), synaptophysin (SYP), and brain-derived neurotrophic factor (BDNF). Besides, neuroinflammatory cytokine levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β as well as microglia activation and oxidative stress damage were attenuated after TNIL treatment in aged mice with PND. Further investigation suggested that TNIL relieved oxidative stress response by activating the SIRT3/AMPK/Nrf2 pathway.ConclusionTranscranial near-infrared laser improved cognitive impairment in aged mice with PND, which may be a promising therapeutic for PND.

Dysregulation of iron homeostasis and ferroptosis in sevoflurane and isoflurane associated perioperative neurocognitive disorders

“…Nrf2 may also impact the occurrence of ferroptosis by inhibiting anesthesia-induced neuroinflammatory responses. 102,103 Hence, Nrf2 may be a potential ferroptosis target for sevoflurane-induced neurotoxicity in offspring.…”

“…In this study, knockdown of Nrf2 inversed the protective effects of echinatin through regulating iron overload, ROS accumulation, lipid peroxidation, and degradation of GPX4. Nrf2 may also impact the occurrence of ferroptosis by inhibiting anesthesia‐induced neuroinflammatory responses 102,103 . Hence, Nrf2 may be a potential ferroptosis target for sevoflurane‐induced neurotoxicity in offspring.…”

Surgery induces neurocognitive disorder via neuroinflammation and glymphatic dysfunction in middle-aged mice with brain lymphatic drainage impairment

“…Furthermore, individuals with PND exhibit a higher risk for developing dementia (Evered et al, 2018;Deiner et al, 2021;He et al, 2024). PND has been associated with increased morbidity and mortality rates, prolonged hospital stays, and diminished quality of life (Zhong et al, 2022;Zeng et al, 2023). In the foreseeable future, surgical treatment will continue to be the primary radical approach for various surgical conditions; hence, it is imperative to enhance postoperative cognitive decline management for the populations with aging, neurodegenerative diseases and cerebrovascular diseases.…”