Critical role of inflammatory cytokines in impairing biochemical processes for learning and memory after surgery in rats

Background: Patients with postoperative cognitive dysfunction have poor outcomes. Neuroinflammation may be the underlying pathophysiology for this dysfunction. We determined whether proinflammatory cytokines affect the trafficking of a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors to the plasma membrane, a fundamental biochemical process for learning and memory. Methods: Four-month-old male Fischer 344 rats were subjected to right carotid exposure under isoflurane anesthesia. Some rats received intravenous lidocaine infusion during anesthesia. Rats were tested two weeks later by Barnes maze. The hippocampus was harvested six hours after the surgery for western blotting of interleukin (IL)-1 beta or IL-6. Hippocampal slices were prepared from control rats or rats subjected to surgery two weeks previously. They were incubated with tetraethylammonium, an agent that can induce long term potentiation, for determining the trafficking of GluR1, an a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit. Results: Surgery or anesthesia increased the time to identify the target box during the Barnes maze test training sessions and one day after the training sessions. Surgery also prolonged the time to identify the target box eight days after the training sessions. Surgery increased IL-1 beta and IL-6 in the hippocampus. The tetraethylammonium-induced GluR1 phosphorylation and trafficking were abolished in the hippocampal slices of rats after surgery. These surgical effects were partly inhibited by lidocaine. The incubation of control hippocampal slices with IL-1 beta and IL-6 abolished tetraethylammonium-induced GluR1 trafficking and phosphorylation. Lidocaine minimally affected the effects of IL-1 beta on GluR1 trafficking. Conclusions: Our results suggest that surgery increases proinflammatory cytokines that then inhibit GluR1 trafficking, leading to learning and memory impairment.