Inhibiting tumor necrosis factor‑α signaling attenuates postoperative cognitive dysfunction in aged rats

Ma,Yuanzhong; Cheng,Qinghao; Wang,Ermin; Li,Lei; Zhang,Xubin

doi:10.3892/mmr.2015.3744

Inhibiting tumor necrosis factor‑α signaling attenuates postoperative cognitive dysfunction in aged rats

Authors:
- Yuanzhong Ma
- Qinghao Cheng
- Ermin Wang
- Lei Li
- Xubin Zhang
View Affiliations

Affiliations: Department of Anesthesiology, Dezhou People's Hospital, Dezhou, Shandong 253045, P.R. China, Department of Anesthesiology, China Meitan General Hospital, Beijing 100028, P.R. China, Department of Orthopedics, Dezhou People's Hospital, Dezhou, Shandong 253045, P.R. China
Published online on: May 7, 2015 https://doi.org/10.3892/mmr.2015.3744
Pages: 3095-3100

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Postoperative cognitive dysfunction (POCD), commonly observed in elderly patients, is characterized by impaired concentration, memory and learning following surgery, and may persist for a long duration or progress into serious central nervous system diseases. It has been demonstrated neuroinflammation caused by surgery is involved in the development of POCD. However, the detailed molecular mechanism remains to be fully elucidated. The present study aimed to reveal the role of tumor necrosis factor (TNF)‑α in the development of POCD in aged rats. Laparotomy was performed to mimic human abdominal surgery in the aged rats. Following surgery, the memory and learning functions were impaired, with significant upregulation of pro‑inflammatory cytokines, including TNF‑α, interleukin (IL)‑1β, IL‑4 and IL‑6 in the hippocampal tissues. However, intracisternal administration of the TNF‑α receptor antagonist, R‑7050, during surgery attenuated these defects in cognitive function and inhibited the production of the pro‑inflammatory cytokines in the hippocampal tissues. Furthermore, intracisternal administration of R‑7050 inhibited the activation of the downstream nuclear factor‑κB and mitogen‑activated protein kinase signaling pathway in the hippocampal tissues. Therefore, the results of the present study suggested a key role of the TNF‑α‑mediated signaling pathway in the development of POCD.

View Figures

View References

1	Colenkova AV, Bondarenko AA, Yu Lubnin A and Dzyubanova NA: Postoperative cognitive dysfunction in elderly patients. Anesteziol Reanimatol. 4:13–19. 2012.In Russian.
2	Li M, Yong-Zhe L, Ya-Qun M, Sheng-Suo Z, Li-Tao Z and Ning-Ling P: Ulinastatin alleviates neuroinflammation but fails to improve cognitive function in aged rats following partial hepatectomy. Neurochem Res. 38:1070–1077. 2013. View Article : Google Scholar : PubMed/NCBI
3	Cao XZ, Ma H, Wang JK, et al: Postoperative cognitive deficits and neuroinflammation in the hippocampus triggered by surgical trauma are exacerbated in aged rats. Prog Neuropsychopharmacol Biol Psychiatry. 34:1426–1432. 2010. View Article : Google Scholar : PubMed/NCBI
4	Chen J, Buchanan JB, Sparkman NL, Godbout JP, Freund GG and Johnson RW: Neuroinflammation and disruption in working memory in aged mice after acute stimulation of the peripheral innate immune system. Brain Behav Immun. 22:301–311. 2008. View Article : Google Scholar
5	Garcia GE, Xia Y, Chen S, et al: NF-kappaB-dependent fractalkine induction in rat aortic endothelial cells stimulated by IL-1beta, TNF-alpha and LPS. J Leukoc Biol. 67:577–584. 2000.PubMed/NCBI
6	Rosczyk HA, Sparkman NL and Johnson RW: Neuroinflammation and cognitive function in aged mice following minor surgery. Exp Gerontol. 43:840–846. 2008. View Article : Google Scholar : PubMed/NCBI
7	Terrando N, Monaco C, Ma D, Foxwell BM, Feldmann M and Maze M: Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. Proc Natl Acad Sci USA. 107:20518–20522. 2010. View Article : Google Scholar : PubMed/NCBI
8	Riches DW, Chan ED and Winston BW: TNF-alpha-induced regulation and signalling in macrophages. Immunobiology. 195:477–490. 1996. View Article : Google Scholar : PubMed/NCBI
9	Yang HL, Chang HC, Lin SW, et al: Antrodia salmonea inhibits TNF-α-induced angiogenesis and atherogenesis in human endothelial cells through the down-regulation of NF-κB and up-regulation of Nrf2 signaling pathways. J Ethnopharmacol. 151:394–406. 2014. View Article : Google Scholar
10	Song HY, Regnier CH, Kirschning CJ, Goeddel DV and Rothe M: Tumor necrosis factor (TNF)-mediated kinase cascades: Bifurcation of nuclear factor-kappaB and c-jun N-terminal kinase (JNK/SAPK) pathways at TNF receptor-associated factor 2. Proc Natl Acad Sci USA. 94:9792–9796. 1997. View Article : Google Scholar : PubMed/NCBI
11	Yuasa T, Ohno S, Kehrl JH and Kyriakis JM: Tumor necrosis factor signaling to stress-activated protein kinase (SAPK)/Jun NH2-terminal kinase (JNK) and p38. Germinal center kinase couples TRAF2 to mitogen-activated protein kinase/ERK kinase kinase 1 and SAPK while receptor interacting protein associates with a mitogen-activated protein kinase kinase kinase upstream of MKK6 and p38. J Biol Chem. 273:22681–22692. 1998. View Article : Google Scholar : PubMed/NCBI
12	Hu Z, Ou Y, Duan K and Jiang X: Inflammation: A bridge between postoperative cognitive dysfunction and Alzheimer’s disease. Med Hypotheses. 74:722–724. 2010. View Article : Google Scholar
13	Yu D, Corbett B, Yan Y, et al: Early cerebrovascular inflammation in a transgenic mouse model of Alzheimer’s disease. Neurobiol Aging. 33:2942–2947. 2012. View Article : Google Scholar : PubMed/NCBI
14	Abildstrom H, Rasmussen LS, Rentowl P, et al: Cognitive dysfunction 1–2 years after non-cardiac surgery in the elderly. ISPOCD group International study of post-operative cognitive dysfunction. Acta Anaesthesiol Scand. 44:1246–1251. 2000. View Article : Google Scholar : PubMed/NCBI
15	Boodhwani M, Rubens FD, Wozny D, et al: Predictors of early neurocognitive deficits in low-risk patients undergoing on-pump coronary artery bypass surgery. Circulation. 114(Suppl 1): I461–I466. 2006. View Article : Google Scholar : PubMed/NCBI
16	Canet J, Raeder J, Rasmussen LS, et al: Cognitive dysfunction after minor surgery in the elderly. Acta Anaesthesiol Scand. 47:1204–1210. 2003. View Article : Google Scholar : PubMed/NCBI
17	Deiner S and Silverstein JH: Postoperative delirium and cognitive dysfunction. Br J Anaesth. 103(Suppl 1): i41–i46. 2009. View Article : Google Scholar : PubMed/NCBI
18	Kamer AR, Galoyan SM, Haile M, et al: Meloxicam improves object recognition memory and modulates glial activation after splenectomy in mice. Eur J Anaesthesiol. 29:332–337. 2012. View Article : Google Scholar : PubMed/NCBI
19	Hains LE, Loram LC, Taylor FR, et al: Prior laparotomy or corticosterone potentiates lipopolysaccharide-induced fever and sickness behaviors. J Neuroimmunol. 239:53–60. 2011. View Article : Google Scholar : PubMed/NCBI
20	Didem B, Huseyin B, Osman Y, Yasemin B, Necati G and Canan T: Early effects of laparotomy and laparoscopy on bacterial behavior and proinflammatory cytokines on bacterial peritonitis in rats I: Escherichia coli. J Pediatr Surg. 43:1494–1501. 2008. View Article : Google Scholar : PubMed/NCBI
21	Kannan S, Saadani-Makki F, Muzik O, et al: Microglial activation in perinatal rabbit brain induced by intrauterine inflammation: Detection with 11C-(R)-PK11195 and small-animal PET. J Nucl Med. 48:946–954. 2007. View Article : Google Scholar : PubMed/NCBI
22	Barrientos RM, Hein AM, Frank MG, Watkins LR and Maier SF: Intracisternal interleukin-1 receptor antagonist prevents postoperative cognitive decline and neuroinflammatory response in aged rats. J Neurosci. 32:14641–14648. 2012. View Article : Google Scholar : PubMed/NCBI
23	Hoesel B and Schmid JA: The complexity of NF-κB signaling in inflammation and cancer. Mol Cancer. 12:862013. View Article : Google Scholar
24	Muñoz A and Costa M: Nutritionally mediated oxidative stress and inflammation. Oxid Med Cell Longev. 2013:6109502013. View Article : Google Scholar : PubMed/NCBI
25	Arslan F, Lai RC, Smeets MB, et al: Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia/reperfusion injury. Stem Cell Res. 10:301–312. 2013. View Article : Google Scholar : PubMed/NCBI
26	Chen WL, Sheu JR, Hsiao CJ, Hsiao SH, Chung CL and Hsiao G: Histone deacetylase inhibitor impairs plasminogen activator inhibitor-1 expression via inhibiting TNF-α-activated MAPK/AP-1 signaling cascade. Biomed Res Int. 2014:2310122014. View Article : Google Scholar
27	Lee IT, Lin CC, Cheng SE, Hsiao LD, Hsiao YC and Yang CM: TNF-alpha induces cytosolic phospholipase A2 expression in human lung epithelial cells via JNK1/2- and p38 MAPK-dependent AP-1 activation. PLoS One. 8:e727832013. View Article : Google Scholar
28	Qiu Q, Xiong W, Yang C, et al: Lymphocyte-derived micropar-ticles induce apoptosis of airway epithelial cells through activation of p38 MAPK and production of arachidonic acid. Apoptosis. 19:1113–1127. 2014. View Article : Google Scholar : PubMed/NCBI
29	Ma JQ, Ding J, Zhang L and Liu CM: Ursolic acid protects mouse liver against CCl4-induced oxidative stress and inflammation by the MAPK/NF-κB pathway. Environ Toxicol Pharmacol. 37:975–983. 2014. View Article : Google Scholar : PubMed/NCBI