Tracking ClO – Dynamics during the Progression of Parkinson’s Disease in MPTP Mouse Model Using In Vivo Brain Microdialysis

Oxidative stress induced by hypochlorite (ClO-) is significant in Parkinson's disease (PD) pathogenesis, yet the dynamic variation in the brain's ClO- level during PD progression remains unclear. Herein, we developed a new reliable method combining in vivo microdialysis brain sampling with fluorescence detection for accurate and real-time tracking of local ClO- levels in the striatum. In the strategy, N,P-co-doped fluorescent carbon dots (N,P-CDs+) with a high positive charge (22.33 mV) and an average particle size (4.4 nm) were synthesized, exhibiting membrane-impermeability, fast response, high selectivity, and good sensitivity toward ClO-. Leveraging the electrostatic attraction between N,P-CDs+ and ClO-, an N,P-CDs+-functionalized microdialysis perfusate for rapid capture of ClO- was constructed, yielding a 6.13-fold enhancement in the microdialysis recovery compared with artificial cerebrospinal fluid (aCSF). Importantly, this is the first report of a sustained elevation of the ClO- level in the striatum of MPTP-induced acute PD model mice for up to 11 h, accompanied by increased expression of the microglia-specific protein IBA1 and the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. Overall, this work provides a powerful analytical method for in vivo detection of ClO-, and simultaneously reveals the variation pattern of the ClO- level in PD pathogenesis.