Nicotine-Induced Neuroprotection against Cognitive Dysfunction after Partial Hepatectomy Involves Activation of BDNF/TrkB Signaling Pathway and Inhibition of NF-κB Signaling Pathway in Aged Rats

Introduction: The main purpose of this study was to investigate the effects and possible mechanisms of nicotine pre-treatment on postoperative cognitive dysfunction (POCD) in aged rats. Methods: Nicotine (0.5 mg/kg) was given i.p. immediately after anesthesia induction. After the Morris water maze test was used to evaluate the rats' spatial learning and memory, serum and hippocampal tissues were harvested 1 and 3 days after intervention. Inflammatory cytokines in the serum were evaluated by Enzyme-linked Immunosorbent Assay (ELISA). Brain-derived neurotrophic factor (BDNF), p-TrkB, neuroinflammation cytokines, NF-kappa B p65, and cleaved caspase-3 were measured by western blotting; neuronal apoptosis in the hippocampal CA1 region was also evaluated by TUNEL staining. Results: We found that nicotine markedly attenuated the POCD and reduced the elevated levels of inflammatory cytokines in the serum, including IL-1 beta and high mobility group box-1 (HMGB1), on postoperative day 1. Additionally, nicotine suppressed the surgery-induced release of IL-1 beta, TNF-alpha, HMGB1, and NF-kappa B p65 in the hippocampus on postoperative day 1 and day 3. In addition, operated rats displayed lower BDNF and p-TrkB in the hippocampus on postoperative day 1, returning to baseline by postoperative day 3. However, nicotine pre-treatment clearly reversed the surgical stress-induced decrease in both BDNF and p-TrkB expression in the hippocampus. Furthermore, nicotine pre-treatment significantly alleviated the surgery-induced increase in the neuronal apoptosis in the hippocampus on postoperative day 1 and day 3. Conclusions: Our results showed that nicotine-induced neuroprotection against POCD may involve activation of the BDNF/TrkB signaling pathway and inhibition of the NF-kappa B signaling pathway.