TY - JOUR T1 - Effect of combined application of nicotine and celecoxib attenuating cognitive impairments by inhibiting inflammation in ischemic rats JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 214 LP - 214 VL - 61 IS - supplement 1 AU - Jinyu Gou AU - Yafu Yin AU - hui wang Y1 - 2020/05/01 UR - http://jnm.snmjournals.org/content/61/supplement_1/214.abstract N2 - 214Introduction: The main objective of this study was to investigate the synergistic anti-inflammation effects of nicotine and celecoxib to improve cognitive impairment in ischemic rats. Methods: Twelve adult Sprague-Dawley (SD) rats underwent ischemic model surgery by injecting endothelin-1 into the left thalamus, which were classified into four different groups with different intervention: nicotine(1.5mg/kg/d), celecoxib(15mg/kg/d), nicotine(1.5mg/kg/d) +celecoxib(15mg/kg/d), or saline, after ischemic model surgery. Another three male SD rats also underwent same surgery, while not injecting endothelin-1 instead of saline, as the control group. Morris water maze (MWM) test was adopted to assess the cognition. All the rats underwent the MWM test, micro positron emission tomography imaging with 2-[18F]-A-85380 for α4β2-nAChRs detection. Results: For all five groups, rats showed shorter and shorter escape latency with each progressive day. The escape latency on the fifth day in the ischemia group was significantly longer than in the control group (p <0.05), and the escape latency in the nicotine, celecoxib or celecoxib + nicotine group was significantly shorter than in the ischemia group (p < 0.05). The escape latency of rats given both nicotine and celecoxib were shorter than in the nicotine or celecoxib group. The difference of escape latency between nicotine and celecoxib groups did not reach statistical significance (p > 0.05). The same results also appeared in probe trial, the times crossing target quadrant and the time in target quadrant in the nicotine group were significantly more or longer than in the ischemia group, and for the ischemia group, the times crossing target quadrant were many fewer and the time in target quadrant was much shorter than the control group (p <0 .05). Rats in the nicotine, celecoxib or both nicotine and celecoxib group showed improved spatial learning and memories. Micro positron emission tomography imaging showed higher uptake of tracer in the left thalamus and whole brain in rat given nicotine, both nicotine and celecoxib than in ischemic rats. Conclusions: Combined application of nicotine and celecoxib can improve cognitive function in ischemic rats, the effect is better than single application of nicotine or celecoxib. Combined application of two drugs with different anti-inflammation mechanism , one is activating α4β2-nAChRs ,the other is cyclooxygenase-2 inhibitor ,could obtain better effect in attenuating cognitive impairment in ischemic rats. ER -