Ischemic Stroke Induces ROS Accumulation, Maladaptive Mitophagy, and Neuronal Apoptosis in Minipigs

Area of Science:

• Neuroscience
• Pathophysiology
• Cell Biology

Background:

• Reactive oxygen species (ROS)-induced mitophagy is crucial in acute ischemic stroke (AIS) pathophysiology.
• Rodent models limit clinical translation; porcine models offer greater relevance.
• Understanding ROS-induced mitophagy in AIS is vital for developing effective treatments.

Purpose of the Study:

• To develop a porcine model of permanent stroke.
• To investigate pathophysiological alterations, focusing on ROS-induced mitophagy after AIS.
• To explore the role of ROS and mitophagy in brain damage and inflammation.

Main Methods:

• Permanent middle cerebral artery occlusion induced via electrocoagulation in miniature pigs.
• Assessment of global brain damage, neuroinflammation, ROS levels, mitophagy, and apoptosis.
• Analysis of ROS production and elimination mechanisms.

Main Results:

• Early neuroinflammatory response observed in the ipsilateral hemisphere.
• Significantly elevated ROS levels in the ipsilateral hemisphere and slightly in the contralateral.
• Mitophagy and apoptosis detected in the ischemic core, linked to ROS accumulation.

Conclusions:

• Porcine models effectively replicate AIS pathophysiology, including ROS-induced mitophagy.
• Elevated ROS and subsequent mitophagy/apoptosis in the ischemic core are key mechanisms in AIS.
• Targeting maladaptive mitophagy in the infarct core presents a promising therapeutic strategy for AIS.