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

Yuanjia Zhang1, Yiqian Zhu2, Jie Wu3

  • 1Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.

Insights

Polyethylene terephthalate microplastics (PET-MPs) worsen ischemic stroke by triggering neuroinflammation and oxidative stress. This study reveals PET-MPs as a significant environmental risk factor for cerebrovascular diseases.

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.