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.