{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T05:31:10Z","timestamp":1792647070200,"version":"4.5.0"},"reference-count":61,"publisher":"Frontiers Media SA","funder":[{"DOI":"10.13039\/501100001786","name":"University of Adelaide","doi-asserted-by":"publisher","award":["HDR Scholarship"],"award-info":[{"award-number":["HDR Scholarship"]}],"id":[{"id":"10.13039\/501100001786","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"DOI":"10.3389\/fneur.2016.00191","type":"journal-article","created":{"date-parts":[[2016,11,7]],"date-time":"2016-11-07T14:57:21Z","timestamp":1478530641000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Disparate Changes in Plasma and Brainstem Cytokine Levels in Adult and Ageing Rats Associated with Age-Related Changes in Facial Motor Neuron Number, Snout Muscle Morphology, and Exploratory Behavior"],"prefix":"10.3389","volume":"7","author":[{"given":"Viythia","family":"Katharesan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin David","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Vink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian Paul","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2016,11,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"44","DOI":"10.3389\/fnagi.2016.00044","article-title":"Response: commentary: age-related neurodegenerative disease research needs aging models","volume":"8","author":"Johnson","year":"2016","journal-title":"Front Aging Neurosci"},{"issue":"1","key":"B2","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/S0306-4522(97)00500-9","article-title":"Motoneuron survival and expression of neuropeptides and neurotrophic factor receptors following axotomy in adult and ageing rats","volume":"84","author":"Johnson","year":"1998","journal-title":"Neuroscience"},{"issue":"2","key":"B3","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/S1385-299X(01)00079-4","article-title":"Rapid estimates of neuron number in the confocal microscope combined with in situ hybridisation and immunocytochemistry","volume":"8","author":"Johnson","year":"2001","journal-title":"Brain Res Brain Res Protoc"},{"issue":"1","key":"B4","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/S0306-4522(02)00762-5","article-title":"Age, diet and injury affect the survival of facial motoneurons","volume":"117","author":"Aperghis","year":"2003","journal-title":"Neuroscience"},{"issue":"1\u20132","key":"B5","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.brainres.2004.02.049","article-title":"Different levels of neuroprotection by two insulin-like growth factor-I splice variants","volume":"1009","author":"Aperghis","year":"2004","journal-title":"Brain Res"},{"key":"B6","article-title":"Age-related differences in the magnitude and time course of motoneuronal death following rat facial nerve avulsion","volume-title":"Neuroscience Meeting Planner","author":"Johnson","year":"2011"},{"issue":"2","key":"B7","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1111\/imm.12233","article-title":"Inflammation in neurodegenerative diseases \u2013 an update","volume":"142","author":"Amor","year":"2014","journal-title":"Immunology"},{"issue":"3","key":"B8","first-page":"254","article-title":"The brain\u2019s aging immune system","volume":"1","author":"Streit","year":"2010","journal-title":"Aging Dis"},{"issue":"5","key":"B9","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1016\/S0889-1591(02)00004-1","article-title":"Low levels of circulating inflammatory cytokines \u2013 do they affect human brain functions?","volume":"16","author":"Pollmacher","year":"2002","journal-title":"Brain Behav Immun"},{"issue":"Suppl 1","key":"B10","doi-asserted-by":"publisher","first-page":"S4","DOI":"10.1093\/gerona\/glu057","article-title":"Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases","volume":"69","author":"Franceschi","year":"2014","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"B11","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1111\/j.1749-6632.2001.tb05662.x","article-title":"The inflammation hypothesis of aging: molecular modulation by calorie restriction","volume":"928","author":"Chung","year":"2001","journal-title":"Ann N Y Acad Sci"},{"issue":"5","key":"B12","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1016\/j.neurobiolaging.2005.03.010","article-title":"Peripheral infection and aging interact to impair hippocampal memory consolidation","volume":"27","author":"Barrientos","year":"2006","journal-title":"Neurobiol Aging"},{"issue":"2","key":"B13","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/0163-7258(95)02033-0","article-title":"Cytokines and their receptors in the central nervous system: physiology, pharmacology, and pathology","volume":"69","author":"Rothwell","year":"1996","journal-title":"Pharmacol Ther"},{"issue":"1","key":"B14","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/S0165-5728(97)00103-3","article-title":"Relative contributions of peripheral and central sources to levels of IL-1 alpha in the cerebral cortex of mice: assessment with species-specific enzyme immunoassays","volume":"79","author":"Banks","year":"1997","journal-title":"J Neuroimmunol"},{"issue":"2","key":"B15","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/S0022-3565(24)29260-0","article-title":"Intravenous human interleukin-1alpha impairs memory processing in mice: dependence on blood-brain barrier transport into posterior division of the septum","volume":"299","author":"Banks","year":"2001","journal-title":"J Pharmacol Exp Ther"},{"issue":"1","key":"B16","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.expneurol.2010.11.014","article-title":"Dysregulated neuronal-microglial cross-talk during aging, stress and inflammation","volume":"233","author":"Jurgens","year":"2012","journal-title":"Exp Neurol"},{"issue":"6","key":"B17","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1016\/j.neurobiolaging.2007.09.001","article-title":"Interleukin-4 mediates the neuroprotective effects of rosiglitazone in the aged brain","volume":"30","author":"Loane","year":"2009","journal-title":"Neurobiol Aging"},{"issue":"8","key":"B18","doi-asserted-by":"publisher","first-page":"e106331","DOI":"10.1371\/journal.pone.0106331","article-title":"Prolonged neuroinflammation after lipopolysaccharide exposure in aged rats","volume":"9","author":"Fu","year":"2014","journal-title":"PLoS One"},{"issue":"1","key":"B19","doi-asserted-by":"publisher","first-page":".e1","DOI":"10.1016\/j.neurobiolaging.2010.05.008","article-title":"Ex vivo cultures of microglia from young and aged rodent brain reveal age-related changes in microglial function","volume":"33","author":"Njie","year":"2012","journal-title":"Neurobiol Aging"},{"issue":"5","key":"B20","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1016\/j.neurobiolaging.2005.03.013","article-title":"mRNA up-regulation of MHC II and pivotal pro-inflammatory genes in normal brain aging","volume":"27","author":"Frank","year":"2006","journal-title":"Neurobiol Aging"},{"issue":"1\u20132","key":"B21","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.jneuroim.2013.12.010","article-title":"Age-associated alterations in the time-dependent profile of pro- and anti-inflammatory proteins within the hippocampus in response to acute exposure to interleukin-1beta","volume":"267","author":"Hopp","year":"2014","journal-title":"J Neuroimmunol"},{"issue":"7258","key":"B22","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1136\/bmj.321.7258.424","article-title":"Th1 and Th2 responses: what are they?","volume":"321","author":"Berger","year":"2000","journal-title":"BMJ"},{"issue":"5","key":"B23","first-page":"414","article-title":"Senescence-accelerated mice (SAMs) as a model for brain aging and immunosenescence","volume":"2","author":"Shimada","year":"2011","journal-title":"Aging Dis"},{"issue":"6","key":"B24","first-page":"624","article-title":"The laboratory rat: relating its age with human\u2019s","volume":"4","author":"Sengupta","year":"2013","journal-title":"Int J Prev Med"},{"issue":"3","key":"B25","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1097\/00001756-199602290-00021","article-title":"Similar age-related changes in two regions of muscle with different properties","volume":"7","author":"Vanden Noven","year":"1996","journal-title":"Neuroreport"},{"issue":"1","key":"B26","doi-asserted-by":"publisher","first-page":"127","DOI":"10.4067\/S0717-95022016000100019","article-title":"Image analysis of oxidative and glycolytic muscle fibers during reperfusion injury by segmentation based on regions","volume":"34","author":"Rosero-Salazar","year":"2016","journal-title":"Int J Morphol"},{"key":"B27","first-page":"1","article-title":"Mood and anxiety related phenotypes in mice: characterization using behavioral tests","volume-title":"The Open Field Test","author":"Gould","year":"2009"},{"issue":"1\u20133","key":"B28","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/S0014-2999(03)01272-X","article-title":"The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review","volume":"463","author":"Prut","year":"2003","journal-title":"Eur J Pharmacol"},{"issue":"9","key":"B29","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1007\/s11095-005-5917-9","article-title":"Bioanalytical method validation for macromolecules in support of pharmacokinetic studies","volume":"22","author":"Smolec","year":"2005","journal-title":"Pharm Res"},{"issue":"3","key":"B30","first-page":"400","article-title":"Development of spontaneous mammary tumors over the life-span of the female Charles River (Sprague-Dawley) rat: the influence of ovariectomy, thyroidectomy, and adrenalectomy-ovariectomy","volume":"26","author":"Durbin","year":"1966","journal-title":"Cancer Res"},{"issue":"6","key":"B31","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1093\/jn\/120.6.598","article-title":"Effect of age and diet on glucose tolerance in Sprague-Dawley rats","volume":"120","author":"McDonald","year":"1990","journal-title":"J Nutr"},{"key":"B32","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.exger.2014.01.024","article-title":"The Frailty syndrome: clinical measurements and basic underpinnings in humans and animals","volume":"54","author":"Mohler","year":"2014","journal-title":"Exp Gerontol"},{"issue":"6","key":"B33","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1093\/gerona\/glt136","article-title":"A clinical frailty index in aging mice: comparisons with frailty index data in humans","volume":"69","author":"Whitehead","year":"2014","journal-title":"J Gerontol A Biol Sci Med Sci"},{"issue":"3","key":"B34","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1007\/s004010050792","article-title":"Enlarged and phagocytic, but not primed, interleukin-1 alpha-immunoreactive microglia increase with age in normal human brain","volume":"95","author":"Sheng","year":"1998","journal-title":"Acta Neuropathol"},{"issue":"4","key":"B35","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1002\/glia.20468","article-title":"Microglia derived from aging mice exhibit an altered inflammatory profile","volume":"55","author":"Sierra","year":"2007","journal-title":"Glia"},{"issue":"2\u20133","key":"B36","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.exger.2010.09.008","article-title":"Cytokines and neuronal channels: a molecular basis for age-related decline of neuronal function?","volume":"46","author":"Viviani","year":"2011","journal-title":"Exp Gerontol"},{"issue":"5","key":"B37","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1002\/ana.410390511","article-title":"Intercellular adhesion molecule-1-deficient mice are less susceptible to cerebral ischemia-reperfusion injury","volume":"39","author":"Soriano","year":"1996","journal-title":"Ann Neurol"},{"issue":"15","key":"B38","doi-asserted-by":"crossref","first-page":"5528","DOI":"10.1523\/JNEUROSCI.21-15-05528.2001","article-title":"Role of IL-1alpha and IL-1beta in ischemic brain damage","volume":"21","author":"Boutin","year":"2001","journal-title":"J Neurosci"},{"issue":"3","key":"B39","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/j.bbi.2007.08.014","article-title":"Neuroinflammation and disruption in working memory in aged mice after acute stimulation of the peripheral innate immune system","volume":"22","author":"Chen","year":"2008","journal-title":"Brain Behav Immun"},{"issue":"10","key":"B40","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1038\/35094583","article-title":"Cytokines and acute neurodegeneration","volume":"2","author":"Allan","year":"2001","journal-title":"Nat Rev Neurosci"},{"issue":"10","key":"B41","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1016\/j.tins.2004.07.011","article-title":"Cytokines and the aging brain \u2013 what we don\u2019t know might help us","volume":"27","author":"Bodles","year":"2004","journal-title":"Trends Neurosci"},{"issue":"2","key":"B42","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.imbio.2011.07.023","article-title":"Complement activation as a biomarker for Alzheimer\u2019s disease","volume":"217","author":"Aiyaz","year":"2012","journal-title":"Immunobiology"},{"issue":"25","key":"B43","doi-asserted-by":"publisher","first-page":"1953","DOI":"10.1016\/0024-3205(92)90112-3","article-title":"Increase of plasma IL-6 concentration with age in healthy subjects","volume":"51","author":"Wei","year":"1992","journal-title":"Life Sci"},{"issue":"7","key":"B44","doi-asserted-by":"publisher","first-page":"M357","DOI":"10.1093\/gerona\/54.7.M357","article-title":"A high plasma concentration of TNF-alpha is associated with dementia in centenarians","volume":"54","author":"Bruunsgaard","year":"1999","journal-title":"J Gerontol A Biol Sci Med Sci"},{"issue":"4","key":"B45","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/S0047-6374(03)00025-3","article-title":"Plasma cytokine profiles in elderly humans","volume":"124","author":"Forsey","year":"2003","journal-title":"Mech Ageing Dev"},{"issue":"12 Pt 2","key":"B46","doi-asserted-by":"publisher","first-page":"S173","DOI":"10.1301\/nr.2007.dec.S173-S176","article-title":"Inflammaging as a major characteristic of old people: can it be prevented or cured?","volume":"65","author":"Franceschi","year":"2007","journal-title":"Nutr Rev"},{"issue":"1\u20133","key":"B47","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.ejphar.2004.07.040","article-title":"Cytokine-induced sickness behaviour: a neuroimmune response to activation of innate immunity","volume":"500","author":"Dantzer","year":"2004","journal-title":"Eur J Pharmacol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1159\/000346362","article-title":"Peripheral inflammation and cognitive aging","volume":"28","author":"Lim","year":"2013","journal-title":"Mod Trends Pharmacopsychiatri"},{"issue":"12","key":"B49","doi-asserted-by":"publisher","first-page":"5052","DOI":"10.1096\/fj.09-150714","article-title":"TNF-\u03b1 impairs regulation of muscle oxidative phenotype: implications for cachexia?","volume":"24","author":"Remels","year":"2010","journal-title":"FASEB J"},{"issue":"5","key":"B50","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.tem.2016.03.002","article-title":"Cytokine signaling in skeletal muscle wasting","volume":"27","author":"Zhou","year":"2016","journal-title":"Trends Endocrinol Metab"},{"issue":"Suppl","key":"B51","first-page":"iii","article-title":"The developmental history of the motor neuron","volume":"15","author":"Hamburger","year":"1977","journal-title":"Neurosci Res Program Bull"},{"issue":"11","key":"B52","first-page":"450","article-title":"Motoneurone survival: a functional approach","volume":"19","author":"Greensmith","year":"1996","journal-title":"Trends Neurosci"},{"key":"B53","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1146\/annurev.ne.14.030191.002321","article-title":"Cell death during development of the nervous system","volume":"14","author":"Oppenheim","year":"1991","journal-title":"Annu Rev Neurosci"},{"issue":"2","key":"B54","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/S0896-6273(00)80151-8","article-title":"Neurotrophic survival molecules for motoneurons: an embarrassment of riches","volume":"17","author":"Oppenheim","year":"1996","journal-title":"Neuron"},{"issue":"4\u20136","key":"B55","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1159\/000156474","article-title":"Neuroinflammation associated with aging sensitizes the brain to the effects of infection or stress","volume":"15","author":"Sparkman","year":"2008","journal-title":"Neuroimmunomodulation"},{"issue":"11","key":"B56","doi-asserted-by":"publisher","first-page":"2484","DOI":"10.1002\/jnr.22074","article-title":"Increased levels of proinflammatory cytokines in the aged rat brain attenuate injury-induced cytokine response after excitotoxic damage","volume":"87","author":"Campuzano","year":"2009","journal-title":"J Neurosci Res"},{"key":"B57","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.mad.2014.06.005","article-title":"Inflamm-aging does not simply reflect increases in pro-inflammatory markers","volume":"139","author":"Morrisette-Thomas","year":"2014","journal-title":"Mech Ageing Dev"},{"issue":"3","key":"B58","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1111\/acel.12065","article-title":"Heterochronic parabiosis: historical perspective and methodological considerations for studies of aging and longevity","volume":"12","author":"Conboy","year":"2013","journal-title":"Aging Cell"},{"key":"B59","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.arr.2014.11.004","article-title":"The systemic milieu as a mediator of dietary influence on stem cell function during ageing","volume":"19","author":"Murphy","year":"2015","journal-title":"Ageing Res Rev"},{"key":"B60","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/1742-2094-5-51","article-title":"Inflammaging as a prodrome to Alzheimer\u2019s disease","volume":"5","author":"Giunta","year":"2008","journal-title":"J Neuroinflammation"},{"issue":"2\u20133","key":"B61","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1007\/s12035-010-8105-9","article-title":"Inflammatory neurodegeneration and mechanisms of microglial killing of neurons","volume":"41","author":"Brown","year":"2010","journal-title":"Mol Neurobiol"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fneur.2016.00191\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T02:25:00Z","timestamp":1749695100000},"score":1,"resource":{"primary":{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fneur.2016.00191\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11,7]]},"references-count":61,"URL":"https:\/\/doi.org\/10.3389\/fneur.2016.00191","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11,7]]}}}