Investigating the effects of systemic immune responses on the infiltration of peripheral macrophages into the brain

Abstract

Postoperative cognitive dysfunction (POCD) is a complication occurring days to months after surgery causing deficits in memory, executive functions and other cognitive abilities. It is especially prevalent among the elderly, which makes it an increasingly important healthcare problem as population aging becomes progressively severe in Hong Kong. A lot of research has been conducted in hopes of uncovering the mechanisms behind POCD, with limited success. Anaesthesia used during surgery was first identified as a cause for the condition, but subsequent studies showed equivocal results which prompted researchers to look at other potential etiologies. Further investigations into the disease revealed that systemic inflammatory response induced by surgical trauma could actually trigger dysfunction in the blood-brain barrier, which had a good correlation with clinical cognitive function impairment. It is suspected that peripheral macrophage infiltration, which was observed in other scenarios of blood-brain-barrier degeneration, might play a part in the systemic immune response after surgery. Thus, this study employs the used of transgenic CD68-EGFP mice with fluorescently tagged peripheral macrophages, in hopes of finding out whether infiltration of peripheral macrophages occurs in systemic immune response triggered by surgery. Although the results showed that there was no significant increased macrophage infiltration in systemic immune response, it was found that certain areas in the hippocampus were subjected to increased macrophage infiltration compared to the frontal cortex even in the absence of systemic immune response, suggesting peripheral macrophage might also play a role in physiological conditions.