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Myocardial Infarction and Functional Outcome Assessment in Pigs
Published on: April 25, 2014
Ischemic Stroke Induces ROS Accumulation, Maladaptive Mitophagy, and Neuronal Apoptosis in Minipigs
Jie Chen1, Yanan Bie2, Yajin Guan1
1Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, South China Institute of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529000, P.R. China.
Abstract:
Reactive oxygen species (ROS)-induced adaptive/maladaptive mitophagy plays an essential role in the pathophysiology of acute ischemic stroke (AIS). However, most studies have been conducted using rodent models, which limits their clinical application. In this study, we aimed to develop porcine models of permanent stroke and observe the pathophysiological alterations caused by acute ischemic stroke, focusing on ROS-induced mitophagy. Miniature pigs were subjected to lateral frontotemporal electrocoagulation, which resulted in permanent middle cerebral artery occlusion. We investigated global brain damage and mechanisms of adaptive/maladaptive mitophagy caused by ROS and global brain inflammation after AIS. An early neuroinflammatory response was observed in the ipsilateral hemisphere. ROS levels were significantly elevated in the ipsilateral hemisphere and slightly elevated in the contralateral hemisphere. ROS accumulation may be attributed to the increased production and impaired elimination of ROS. In addition, mitophagy and apoptosis were detected in the ischemic core, which may be attributed to ROS accumulation. We propose "distinct-area targeting" interventions aimed at maladaptive mitophagy within the ischemic core of the infarct hemisphere, which may provide new therapeutic targets for the treatment of AIS.
Insights
This study developed a porcine model for acute ischemic stroke (AIS) to investigate reactive oxygen species (ROS)-induced mitophagy. Findings reveal elevated ROS and mitophagy in stroke-affected brain areas, suggesting new therapeutic targets.
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.
