Mice with pre-existing tumors are vulnerable to postoperative cognitive dysfunction

Area of Science:

• Neuroscience
• Oncology
• Immunology

Background:

• Postoperative cognitive dysfunction (POCD) is a common complication impacting quality of life, particularly in aging populations undergoing cancer surgery.
• Limited research exists on POCD specifically in cancer patients, despite the increasing prevalence of surgery in this demographic.
• Understanding the mechanisms behind POCD in cancer patients is crucial for developing targeted interventions.

Purpose of the Study:

• To investigate the impact of surgery on cognitive function in tumor-bearing mice.
• To identify potential mechanisms underlying cognitive impairment in these animals.
• To establish a preclinical model for studying cancer-associated POCD.

Main Methods:

• A murine model was established by implanting MC38 colon cancer cells and subsequently performing tibial fracture surgery.
• Cognitive function was assessed using the Morris water maze (MWM) and novel object recognition (NOR) tests.
• Hippocampal PSD-95 expression, plasma and hippocampal cytokine levels (TNF-α, IL-6, IL-1β), microglia activation, and blood-brain barrier (BBB) permeability were analyzed.

Main Results:

• Tumor-bearing mice exhibited significant cognitive impairment post-surgery, unlike mice with surgery or tumors alone.
• Elevated plasma and hippocampal levels of TNF-α, IL-6, and IL-1β were observed in tumor-bearing mice post-surgery.
• Increased BBB permeability and absence of hippocampal microglia activation were noted in tumor-bearing mice.

Conclusions:

• Mice with tumors are more susceptible to developing postoperative cognitive dysfunction (POCD).
• Prolonged central inflammation, potentially originating from peripheral immunity, appears to underlie surgical cognitive impairment in tumor-bearing mice.
• This model provides insights into the mechanisms of cancer-related POCD and highlights the role of systemic inflammation.