Low-dose ciprofol attenuates motor dysfunction in PD mice by inhibiting NLRP3 inflammasome activation

With the increasing prevalence of Parkinson's disease (PD) patients, the surgical demand among PD patients is concurrently expanding. Some anesthetics have been reported to exert protective effects against PD progression, whereas others have not exhibited such effects. Ciprofol, a novel intravenous anesthetic, shares structural similarities with propofol and is considered more suitable for elderly individuals. Nevertheless, its effect on PD progression remains elusive. In the present study, low-dose ciprofol did not induce narcosis, improved motor deficits in PD mice, and attenuated dopaminergic neuronal degeneration. Moreover, ciprofol administered at doses sufficient to cause narcosis did not accelerate PD progression. Low-dose ciprofol inhibited the microglial expression of NLRP3, cl-caspase-1, and the levels of IL-18, IL-1β in the substantia nigra pars compacta and striatum. Furthermore, the NLRP3 agonist nigericin suppressed the anti-inflammatory and neuroprotective effects of low-dose ciprofol in BV2 and SH-SY5Y cells. Overall, these results indicated that low-dose ciprofol protected dopaminergic neurons and ameliorated motor impairments in MPTP-induced PD mice, potentially by inhibiting microglial NLRP3 inflammasome. These findings support its clinical use and offer valuable insights into the neurobiological mechanisms by which anesthetics modulate PD progression.