Postoperative cognitive deficits and neuroinflammation in the hippocampus triggered by surgical trauma are exacerbated in aged rats

Postoperative cognitive dysfunction (POCD) is characterized by the progressive deterioration of intellectual/cognitive function following surgery. It has been suggested that the senile brain, which characteristically expresses higher levels of central proinflammatory cytokines, interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α, is more susceptible to additional insult following surgery. The authors of this study investigated the expression of central cytokines IL-1β, IL-6 and TNF-α and hippocampal glial cell activation in aged and adult rats following partial hepatectomy.Cognitive function was assessed in a reversal-learning version of the Morris water maze (MWM) before and after surgery. Hippocampal pro-inflammatory cytokines IL-1β, IL-6 and TNF-α and glial cell activation markers glial fibrillary acidic protein (GFAP) and S100β were measured at each time point; CD200 and CD200R were also measured to explore potential mechanisms of glial cell activation.Surgical trauma resulted in impairments in distance and latency only on postoperative day 1 (p < 0.001, respectively) in adult rats. Aged rats exhibited impairments on day 1 (p < 0.001) that persisted until postoperative day 3 (p = 0.002 and p = 0.001, respectively). All significant impairments paralleled upregulated cytokine IL-1β and IL-6 expression. Immunohistochemistry assay further showed more hippocampal glial cell activation in aged rats compared to that in adults.Overall, these findings suggest that surgical trauma, rather than anesthesia, resulted in cognitive function impairment potentiated by aging. Hippocampal pro-inflammatory cytokines and glial cell activation might mediate trauma-induced POCD.

Research Highlights
► Moderate surgical trauma induced an exaggerated neuroinflammatory response and an exacerbated cognitive impairment in aged rats when compared to their adult counterparts.
► Anesthesia alone did not impair cognitive function or alter hippocampal pro-inflammatory cytokine levels in adult and aged rats.
► An age-related increase in susceptibility to cognitive impairments following surgical trauma.