Rosuvastatin Nanomicelles Target Neuroinflammation and Improve Neurological Deficit in a Mouse Model of Intracerebral Hemorrhage

Background: Intracerebral hemorrhage (ICH), a devastating subtype of stroke, has a poor prognosis. However, there is no effective therapy currently available due to its complex pathological progression, in which neuroinflammation plays a pivotal role in secondary brain injury. In this work, the use of statin-loaded nanomicelles to target the neuroinflammation and improve the efficacy was studied in a mouse model of ICH. Methods: Rosuvastatin-loaded nanomicelles were prepared by a co-solvent evaporation method using polyethylene glycol-poly(e-caprolactone) (PEG-PCL) copolymer as a carrier. The prepared nanomicelles were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS), and then in vitro and in vivo studies were performed. Results: TEM shows that the nanomicelles are spherical with a diameter of about 19.41 nm, and DLS shows that the size, zeta potential, and polymer dispersity index of the nanomicelles were 23.37 nm, -19.2 mV, and 0.221, respectively. The drug loading content is 8.28%. The in vivo study showed that the nanomicelles significantly reduced neuron degeneration, inhibited the inflammatory cell infiltration, reduced the brain edema, and improved neurological deficit. Furthermore, it was observed that the nanomicelles promoted the polarization of microglia/macrophages to M2 phenotype, and also the expression of the proinflammatory cytokines, such as IL-1 beta and TNF-alpha, was significantly down-regulated, while the expression of the anti-inflammatory cytokine IL-10 was significantly up-regulated. The related mechanism was proposed and discussed. Conclusion: The nanomicelles treatment suppressed the neuroinflammation that might contribute to the promoted nerve functional recovery of the ICH mouse, making it potential to be applied in clinic.

Automated summary

This study developed rosuvastatin-loaded nanomicelles to target neuroinflammation in a mouse model of ICH, which significantly reduced neuron degeneration, inhibited inflammatory cell infiltration, reduced brain edema, and improved neurological deficits. The nanomicelles also promoted the polarization of microglia/macrophages to M2 phenotype and down-regulated proinflammatory cytokines while up-regulating anti-inflammatory cytokines, suggesting potential clinical application for promoting nerve functional recovery in ICH.