Abstract
Systemic inflammation can trigger transient or longer-lasting cognitive impairments, particularly in elderly patients. However, its pathogenesis has not been sufficiently clarified. In this study, we explored the potential effects of multisensory rehabilitation on cognitive dysfunction following systemic inflammation using an animal model. Aged male Wister rats were randomly injected intraperitoneally with either saline (control) or lipopolysaccharide (LPS; 5 mg/kg). After injection, both groups of rats were randomly assigned to either of two housing conditions (n = 8 in each condition): a standard cage environment (SC group) or a multisensory early rehabilitation environment (ER group). Cognitive function was examined after 7 days in the assigned environmental condition using a novel object recognition test. In the SC group, the LPS-treated rats showed impaired cognitive function compared with the control animals. These memory deficits were positively correlated with the levels of both tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the hippocampus. On the other hand, in the LPS-treated ER group, neither cognitive impairment nor an increase in hippocampal levels of both TNF-α and IL-1β was found. These results imply that early rehabilitation (ER) intervention may be effective in preventing cognitive dysfunction following systemic inflammation via its anti-neuroinflammatory effects.
References
Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010;304:1787–94.
Sanders RD, Pandharipande PP, Davidson AJ, Ma D, Maze M. Anticipating and managing postoperative delirium and cognitive decline in adults. BMJ. 2011;343:d4331.
Murray C, Sanderson DJ, Barkus C, Deacon RM, Rawlins JN, Bannerman DM, Cunningham C. Systemic inflammation induces acute working memory deficits in the primed brain: relevance for delirium. Neurobiol Aging. 2012;33:603–16.
Witlox J, Eurelings LS, de Jonghe JF, Kalisvaart KJ, Eikelenboom P, van Gool WA. Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis. JAMA. 2010;304:443–51.
Steinmetz J, Christensen KB, Lund T, Lohse N, Rasmussen LS, ISPOCD Group. Long-term consequences of postoperative cognitive dysfunction. Anesthesiology. 2009;110:548–55.
Perry VH, Cunningham C, Holmes C. Systemic infections and inflammation affect chronic neurodegeneration. Nat Rev Immunol. 2007;7:161–7.
Terrando N, Monaco C, Ma D, Foxwell BM, Feldmann M, Maze M. Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. Proc Natl Acad Sci USA. 2010;107:20518–22.
Wilson CJ, Finch CE, Cohen HJ. Cytokines and cognition—the case for a head-to-toe inflammatory paradigm. J Am Geriatr Soc. 2002;50:2041–56.
Nithianantharajah J, Hannan AJ. Enriched environments, experience-dependent plasticity and disorders of the nervous system. Nat Rev Neurosci. 2006;7:697–709.
Woods JA, Vieira VJ, Keylock KT. Exercise, inflammation, and innate immunity. Neurol Clin. 2006;24:585–99.
Barr J, Fraser GL, Puntillo K, Ely EW, Gélinas C, Dasta JF, Davidson JE, Devlin JW, Kress JP, Joffe AM, Coursin DB, Herr DL, Tung A, Robinson BR, Fontaine DK, Ramsay MA, Riker RR, Sessler CN, Pun B, Skrobik Y, Jaeschke R, American College of Critical Care Medicine. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013;41:263–306.
Bossù P, Cutuli D, Palladino I, Caporali P, Angelucci F, Laricchiuta D, Gelfo F, De Bartolo P, Caltagirone C, Petrosini L. A single intraperitoneal injection of endotoxin in rats induces long-lasting modifications in behavior and brain protein levels of TNF-α and IL-18. J Neuroinflammation. 2012;9:101.
Prins ML, Hales A, Reger M, Giza CC, Hovda DA. Repeat traumatic brain injury in the juvenile rat is associated with increased axonal injury and cognitive impairments. Dev Neurosci. 2010;32:510–8.
Lynch MA. Age-related neuroinflammatory changes negatively impact on neuronal function. Front Aging Neurosci. 2010;1:6.
Huang ZB, Sheng GQ. Interleukin-1β with learning and memory. Neurosci Bull. 2010;26:455–68.
Sparkman NL, Johnson RW. Neuroinflammation associated with aging sensitizes the brain to the effects of infection or stress. Neuroimmunomodulation. 2008;15:323–30.
Gordon SM, Jackson JC, Ely EW, Burger C, Hopkins RO. Clinical identification of cognitive impairment in ICU survivors: insights for intensivists. Intensive Care Med. 2004;30:1997–2008.
Kovesdi E, Gyorgy AB, Kwon SK, Wingo DL, Kamnaksh A, Long JB, Kasper CE, Agoston DV. The effect of enriched environment on the outcome of traumatic brain injury; a behavioral, proteomics, and histological study. Front Neurosci. 2011;5:42.
Ruscher K, Johannesson E, Brugiere E, Erickson A, Rickhag M, Wieloch T. Enriched environment reduces apolipoprotein E (ApoE) in reactive astrocytes and attenuates inflammation of the peri-infarct tissue after experimental stroke. J Cereb Blood Flow Metab. 2009;29:1796–805.
Schweickert WD, Pohlman MC, Pohlman AS, Nigos C, Pawlik AJ, Esbrook CL, Spears L, Miller M, Franczyk M, Deprizio D, Schmidt GA, Bowman A, Barr R, McCallister KE, Hall JB, Kress JP. Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet. 2009;373:1874–82.
Simpson J, Kelly JP. The impact of environmental enrichment in laboratory rats: behavioural and neurochemical aspects. Behav Brain Res. 2011;222:246–64.
Maegele M, Lippert-Gruener M, Ester-Bode T, Garbe J, Bouillon B, Neugebauer E, Klug N, Lefering R, Neiss WF, Angelov DN. Multimodal early onset stimulation combined with enriched environment is associated with reduced CNS lesion volume and enhanced reversal of neuromotor dysfunction after traumatic brain injury in rats. Eur J Neurosci. 2005;21:2406–18.
Qin L, Wu X, Block ML, Liu Y, Breese GR, Hong JS, Knapp DJ, Crews FT. Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia. 2007;55:453–62.
Steinman L. Modulation of postoperative cognitive decline via blockade of inflammatory cytokines outside the brain. Proc Natl Acad Sci USA. 2010;107:20595–6.
Streit WJ, Mrak RE, Griffin WS. Microglia and neuroinflammation: a pathological perspective. J Neuroinflammation. 2004;1:14.
Norden DM, Godbout JP. Review: microglia of the aged brain: primed to be activated and resistant to regulation. Neuropathol Appl Neurobiol. 2013;39:19–34.
Makar TK, Bever CT, Singh IS, Royal W, Sahu SN, Sura TP, Sultana S, Sura KT, Patel N, Dhib-Jalbut S, Trisler D. Brain-derived neurotrophic factor gene delivery in an animal model of multiple sclerosis using bone marrow stem cells as a vehicle. J Neuroimmunol. 2009;210:40–51.
Jiang Y, Wei N, Lu T, Zhu J, Xu G, Liu X. Intranasal brain-derived neurotrophic factor protects brain from ischemic insult via modulating local inflammation in rats. Neuroscience. 2011;172:398–405.
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Kawano, T., Morikawa, A., Imori, S. et al. Preventive effects of multisensory rehabilitation on development of cognitive dysfunction following systemic inflammation in aged rats. J Anesth 28, 780–784 (2014). https://doi.org/10.1007/s00540-013-1786-2
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DOI: https://doi.org/10.1007/s00540-013-1786-2