Mechanistic Insights into PET-MPs-Aggravated Ischemic Stroke via Integrated Computational-Experimental Approaches

Area of Science:

• Environmental Science
• Toxicology
• Neuroscience

Background:

• Microplastics, particularly polyethylene terephthalate microplastics (PET-MPs), are widespread environmental pollutants.
• Concerns are growing regarding their potential impact on nervous system health, with evidence of their presence in human brain tissue.
• The specific role of PET-MPs in cerebrovascular diseases like ischemic stroke is not well understood.

Purpose of the Study:

• To investigate how PET-MP exposure exacerbates ischemic stroke.
• To delineate the underlying molecular and cellular mechanisms.
• To assess PET-MPs as an environmental risk factor for cerebrovascular diseases.

Main Methods:

• An integrated framework combining network toxicology, machine learning, and molecular docking.
• Experimental validation using mouse models of cerebral ischemia (middle cerebral artery occlusion) and in vitro models (oxygen-glucose deprivation/reperfusion in BV2 microglial cells).

Main Results:

• Computational analyses identified 15 core target genes linking PET-MP exposure to neuroinflammation and oxidative stress pathways.
• PET-MP exposure significantly worsened cerebral infarction and neurological deficits in mice.
• PET-MP exposure exacerbated microglia-mediated neuroinflammation and oxidative damage in experimental models.

Conclusions:

• PET-MPs act as an environmental risk factor that can worsen ischemic stroke pathology.
• This study provides crucial mechanistic insights into the environmental health risks associated with microplastic pollution.
• Findings highlight the need for further assessment of microplastics' impact on neurological health.