Isoflurane induces learning impairment that is mediated by interleukin 1β in rodents
Lin Cao, Liaoliao Li, Daowei Lin, Zhiyi Zuo, Lin Cao, Liaoliao Li, Daowei Lin, Zhiyi Zuo
Abstract
Postoperative cognitive decline is a clinical syndrome. Volatile anesthetics are commonly used during surgery. It is conceivable that volatile anesthetics may contribute to postoperative cognitive decline. Isoflurane can impair cognitive functions of animals under certain conditions. However, the mechanisms for this impairment are not clear. Here, male 18-month old Fisher 344 rats or 10-week old mice were exposed to 1.2 or 1.4% isoflurane for 2 h. Our studies showed that isoflurane impaired the cognitive functions of the rats in Barnes maze. Isoflurane-exposed rats had reduced freezing behavior during the training sessions in the fear conditioning test. This isoflurane effect was attenuated by lidocaine, a local anesthetic with anti-inflammatory property. Rats that had training sessions and were exposed to isoflurane 30 min later had freezing behavior similar to that of control animals. Isoflurane increased the expression of interleukin 1β (IL-1β), interleukin-6 and activated caspase 3 in the hippocampus of the 18-month old rats. IL-1β positive staining was co-localized with that of NeuN, a neuronal marker. The increase of IL-1β and activated caspase 3 but not interleukin-6 was attenuated by lidocaine. Isoflurane also impaired the cognitive functions of 10-week old C57BL/6J mice and increased IL-1β in their hippocampi. However, isoflurane did not affect the cognitive functions of IL-1β deficient mice. Our results suggest that isoflurane impairs the learning but may not affect the recall of the aged rats. IL-1β may play an important role in this isoflurane effect.
Conflict of interest statement
Competing Interests: The authors have declared that no competing interests exist.
Figures
References
- Silva AC, ORyan F, Poor DB (2006) Postoperative nausea and vomiting (PONV) after orthognathic surgery: a retrospective study and literature review. J Oral Maxillofac Surg 64: 1385–1397.
- Zheng S, Zuo Z (2004) Isoflurane preconditioning induces neuroprotection against ischemia via activation of p38 mitogen-activated protein kinase. Mol Pharmacol 65: 1172–1180.
- Lin D, Zuo Z (2011) Isoflurane induces hippocampal cell injury and cognitive impairments in adult rats. Neuropharmacology 61: 1354–1359.
- Culley DJ, Baxter M, Yukhananov R, Crosby G (2003) The memory effects of general anesthesia persist for weeks in young and aged rats. Anesth Analg 96: 1004–1009.
- Baranov D, Bickler PE, Crosby GJ, Culley DJ, Eckenhoff MF, et al. (2009) Consensus statement: First International Workshop on Anesthetics and Alzheimer’s disease. Anesth Analg 108: 1627–1630.
- Steinmetz J, Christensen KB, Lund T, Lohse N, Rasmussen LS (2009) Long-term consequences of postoperative cognitive dysfunction. Anesthesiology 110: 548–555.
- Monk TG, Weldon BC, Garvan CW, Dede DE, van der Aa MT, et al. (2008) Predictors of cognitive dysfunction after major noncardiac surgery. Anesthesiology 108: 18–30.
- Moller JT, Cluitmans P, Rasmussen LS, Houx P, Rasmussen H, et al. (1998) Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet 351: 857–861.
- Sanderson DJ, Cunningham C, Deacon RM, Bannerman DM, Perry VH, et al. (2009) A double dissociation between the effects of sub-pyrogenic systemic inflammation and hippocampal lesions on learning. Behav Brain Res 201: 103–111.
- Terrando N, Monaco C, Ma D, Foxwell BM, Feldmann M, et al. (2010) Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. Proc Natl Acad Sci U S A 107: 20518–20522.
- Cibelli M, Fidalgo AR, Terrando N, Ma D, Monaco C, et al. (2010) Role of interleukin-1beta in postoperative cognitive dysfunction. Ann Neurol 68: 360–368.
- Wu X, Lu Y, Dong Y, Zhang G, Zhang Y, et al. (2012) The inhalation anesthetic isoflurane increases levels of proinflammatory TNF-alpha, IL-6, and IL-1beta. Neurobiol Aging 33: 1364–1378.
- Lin D, Cao L, Wang Z, Li J, Washington JM, et al. (2012) Lidocaine attenuates cognitive impairment after isoflurane anesthesia in old rats. Behav Brain Res 228: 319–327.
- Caracas HC, Maciel JV, Martins PM, de Souza MM, Maia LC (2009) The use of lidocaine as an anti-inflammatory substance: a systematic review. J Dent 37: 93–97.
- Zhao P, Zuo Z (2004) Isoflurane preconditioning induces neuroprotection that is inducible nitric oxide synthase-dependent in the neonatal rats. Anesthesiology 101: 695–702.
- Zhou Z, Kozlowski J, Schuster DP (2005) Physiologic, biochemical, and imaging characterization of acute lung injury in mice. Am J Respir Crit Care Med 172: 344–351.
- Stratmann G, Sall JW, Bell JS, Alvi RS, May LV, et al. (2010) Isoflurane does not affect brain cell death, hippocampal neurogenesis, or long-term neurocognitive outcome in aged rats. Anesthesiology 112: 305–315.
- Komatsu H, Nogaya J, Anabuki D, Yokono S, Kinoshita H, et al. (1993) Memory facilitation by posttraining exposure to halothane, enflurane, and isoflurane in ddN mice. Anesth Analg 76: 609–612.
- Rammes G, Starker LK, Haseneder R, Berkmann J, Plack A, et al. (2009) Isoflurane anaesthesia reversibly improves cognitive function and long-term potentiation (LTP) via an up-regulation in NMDA receptor 2B subunit expression. Neuropharmacology 56: 626–636.
- Xie Z, Culley DJ, Dong Y, Zhang G, Zhang B, et al. (2008) The common inhalation anesthetic isoflurane induces caspase activation and increases amyloid beta-protein level in vivo. Ann Neurol 64: 618–627.
- Vizcaychipi MP, Xu L, Barreto GE, Ma D, Maze M, et al. (2011) Heat shock protein 72 overexpression prevents early postoperative memory decline after orthopedic surgery under general anesthesia in mice. Anesthesiology 114: 891–900.
- Fidalgo AR, Cibelli M, White JP, Nagy I, Wan Y, et al. (2012) Isoflurane causes neocortical but not hippocampal-dependent memory impairment in mice. Acta Anaesthesiol Scand 56: 1052–1057.
- Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S (2011) The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta 1813: 878–888.
- Xing Z, Gauldie J, Cox G, Baumann H, Jordana M, et al. (1998) IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses. J Clin Invest 101: 311–320.
- Wright CB, Sacco RL, Rundek TR, Delman JB, Rabbani LE, et al. (2006) Interleukin-6 is associated with cognitive function: the Northern Manhattan Study. J Stroke Cerebrovasc Dis 15: 34–38.
- Weaver JD, Huang MH, Albert M, Harris T, Rowe JW, et al. (2002) Interleukin-6 and risk of cognitive decline: MacArthur studies of successful aging. Neurology 59: 371–378.
- Xie Z, Dong Y, Maeda U, Moir RD, Xia W, et al. (2007) The inhalation anesthetic isoflurane induces a vicious cycle of apoptosis and amyloid beta-protein accumulation. J Neurosci 27: 1247–1254.
- Li L, Peng L, Zuo Z (2008) Isoflurane preconditioning increases B-cell lymphoma-2 expression and reduces cytochrome c release from the mitochondria in the ischemic penumbra of rat brain. Eur J Pharmacol 586: 106–113.
- Lahat A, Ben-Horin S, Lang A, Fudim E, Picard O, et al. (2008) Lidocaine down-regulates nuclear factor-kappaB signalling and inhibits cytokine production and T cell proliferation. Clin Exp Immunol 152: 320–327.
- Pardridge WM, Sakiyama R, Fierer G (1983) Transport of propranolol and lidocaine through the rat blood-brain barrier: Primary role of globulin-bound drug. J Clin Invest 71: 900–908.
- Terrando N, Eriksson LI, Ryu JK, Yang T, Monaco C, et al. (2011) Resolving postoperative neuroinflammation and cognitive decline. Ann Neurol 70: 986–995.
- Dickstein RA, Kiremidjian-Schumacher L, Stotzky G (1984) Effect of lidocaine on production of migration inhibitory factor and on macrophage motility: in vitro exposure of guinea pig lymphocytes and macrophages. J Leukoc Biol 36: 621–632.
- Lynch MA (1998) Age-related impairment in long-term potentiation in hippocampus: a role for the cytokine, interleukin-1 beta? Prog Neurobiol 56: 571–589.
- Lee JJ, Li L, Jung HH, Zuo Z (2008) Postconditioning with isoflurane reduced ischemia-induced brain injury in rats. Anesthesiology 108: 1055–1062.
- Kim JJ, Fanselow MS (1992) Modality-specific retrograde amnesia of fear. Science 256: 675–677.
- Li J, Deng J, Sheng W, Zuo Z (2012) Metformin attenuates Alzheimer’s disease-like neuropathology in obese, leptin-resistant mice. Pharmacol Biochem Behav 101: 564–574.
Source: PubMed