Targeting Mitochondria for Postoperative Cognitive Dysfunction: From Mechanisms to Therapeutics

Area of Science:

• Neuroscience
• Gerontology
• Mitochondrial Biology

Background:

• Postoperative cognitive dysfunction (POCD) is a common neurological complication in older adults after surgery.
• POCD leads to significant quality of life decline and societal burden.
• Mitochondrial dysfunction is increasingly recognized as a key factor in POCD pathogenesis.

Purpose of the Study:

• To provide a comprehensive review of the role of mitochondrial dysfunction in POCD.
• To examine current and emerging mitochondria-targeted therapeutic strategies for POCD.
• To discuss challenges and future directions for clinical translation of POCD treatments.

Main Methods:

• Literature review of preclinical and clinical studies on POCD and mitochondrial function.
• Analysis of mechanisms linking mitochondrial impairments to neuroinflammation and cell death.
• Evaluation of mitochondria-targeted drugs (e.g., SS-31, Mdivi-1) and therapeutic approaches.

Main Results:

• Mitochondrial dysfunction in POCD involves disrupted energy metabolism, oxidative stress, calcium imbalance, and altered dynamics.
• These impairments activate neuroinflammation and cell death pathways.
• Preclinical studies show neuroprotective effects of agents like SS-31, Mdivi-1, P110, and NLRP3 inhibitors.

Conclusions:

• Mitochondrial dysfunction is a critical driver of POCD.
• Mitochondria-targeted therapies, including combination and personalized approaches, show therapeutic potential.
• Overcoming barriers like blood-brain barrier penetration is crucial for clinical translation, with nanocarriers and AI offering future solutions.