Pyrrolidine dithiocarbamate attenuates surgery-induced neuroinflammation and cognitive dysfunction possibly via inhibition of nuclear factor κB.
Pyrrolidine dithiocarbamate attenuates surgery-induced neuroinflammation and cognitive dysfunction possibly via inhibition of nuclear factor κB.
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DOI：
10.1016/j.neuroscience.2013.12.034
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发表时间：
2014-03-07
期刊：
影响因子：
3.3
通讯作者：
Zuo, Z.
中科院分区：
文献类型：
--
作者：
Zhang, J.;Jiang, W.;Zuo, Z.
Surgery induces learning and memory impairment. Neuroinflammation may contribute to this impairment. Nuclear factor κB (NF-κB) is an important transcription factor to regulate the expression of inflammatory cytokines. We hypothesize that inhibition of NF-κB by pyrrolidine dithiocarbamate (PDTC) reduces neuroinflammation and the impairment of learning and memory. To test this hypothesis, four-month old male Fischer 344 rats were subjected to right carotid exploration under propofol and buprenorphine anesthesia. Some rats received two doses of 50 mg/kg PDTC given intraperitoneally 30 min before and 6 h after the surgery. Rats were tested in the Barnes maze and fear conditioning paradigm begun 6 days after the surgery. Expression of various proteins related to inflammation was examined in the hippocampus at 24 h or 21 days after the surgery. Here, surgery, but not anesthesia alone, had a significant effect on prolonging the time needed to identify the target hole during the training sessions of Barnes maze. Surgery also increased the time for identifying the target hole in the long-term memory test and decreased context-related learning and memory in fear conditioning test. Also, surgery increased nuclear expression of p65, a NF-κB component, decreased cytoplasmic amount of inhibitor of NF-κB, and increased the expression of interleukin-1β, interleukin-6, ionized calcium binding adaptor molecule 1 and active matrix metalloproteinase 9. Finally, surgery enhanced IgG extravasation in the hippocampus. These surgical effects were attenuated by PDTC. These results suggest that surgery, but not propofol-based anesthesia, induces neuroinflammation and impairment of learning and memory. PDTC attenuates these effects possibly by inhibiting NF-κB activation and the downstream matrix metalloproteinase 9 activity.
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影响因子：
2.7
作者：
Lin, Daowei;Cao, Lin;Wang, Zhi;Li, Jiejie;Washington, Jacqueline M.;Zuo, Zhiyi
通讯作者：
Zuo, Zhiyi
影响因子：
15.3
作者：
SCHRECK, R;MEIER, B;MANNEL, DN;DROGE, W;BAEUERLE, PA
通讯作者：
BAEUERLE, PA
DOI：
10.1523/jneurosci.2173-12.2012
发表时间：
2012-10-17
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Barrientos RM;Hein AM;Frank MG;Watkins LR;Maier SF
通讯作者：
Maier SF
影响因子：
6.2
作者：
Mishra, Anjuli;Kim, Hee Jung;Shin, Angela H.;Thayer, Stanley A.
通讯作者：
Thayer, Stanley A.
影响因子：
11.1
作者：
Mooijaart, S. P.;Sattar, N.;de Craen, A. J. M.
通讯作者：
de Craen, A. J. M.