Iron Oxide Nanozyme as Reactive Oxygen and Nitrogen Species Scavenger to Regulate Microglial Homeostasis in Stroke

Area of Science:

• Nanomedicine
• Neuroscience
• Biochemistry

Background:

• Ischemic stroke triggers pro-inflammatory M1 microglia, leading to excessive nitric oxide (NO) production.
• Elevated NO levels cause apoptosis and disrupt brain tissue, impairing function.
• Current treatments have limitations in addressing the inflammatory cascade post-stroke.

Purpose of the Study:

• To investigate the therapeutic potential of iron oxide nanoparticles (IONPs) in mitigating ischemic stroke injury.
• To evaluate the ability of IONPs to scavenge nitric oxide (NO) and modulate microglial polarization.
• To explore the underlying molecular mechanisms involving the HIF-1α/TIM-3 signaling axis.

Main Methods:

• Utilized 6 nm iron oxide nanoparticles (IONP6) with intrinsic superoxide dismutase (SOD) and catalase (CAT) activities.
• Assessed NO scavenging by forming nitrosyl-metal complexes.
• Evaluated IONP6 efficacy in vitro (oxygen-glucose deprivation) and in vivo (permanent middle cerebral artery occlusion) stroke models.
• Analyzed microglial polarization and modulation of the HIF-1α/TIM-3 signaling pathway.

Main Results:

• IONP6 demonstrated effective scavenging of NO and reactive oxygen and nitrogen species (RONS).
• IONP6 promoted microglial M2 polarization, reducing neuroinflammation in both in vitro and in vivo models.
• Administration of IONP6 significantly reduced infarct size and improved neurological function in stroke rats.
• IONP6 modulated the HIF-1α/TIM-3 signaling axis in stroke models.

Conclusions:

• IONP6 acts as a potent NO scavenger and anti-inflammatory agent for ischemic stroke.
• IONP6 effectively shifts microglial phenotype from M1 to M2, mitigating secondary brain injury.
• IONP6 represents a promising, drug-free therapeutic strategy for stroke treatment by targeting neuroinflammation.