Dr. Colm Cunningham

• Cox, D. J., Field, R. H., Williams, D. G., Baran, M., Bowie, A. G., Cunningham, C. and Dunne, A. , DNA sensors are expressed in astrocytes and microglia in vitro and are upregulated during gliosis in neurodegenerative disease, GLIA, 63, (5), 2015, p812-825Journal Article, 2015, DOI , TARA - Full Text
• Colm Cunningham and Edel Hennessy , Co-morbidity and systemic inflammation as drivers of cognitive decline: new experimental models adopting a broader paradigm in dementia research , Alzheimer's Research & Therapy, 7, 2015, p33-Journal Article, 2015, DOI , TARA - Full Text
• Boustani, M. Rudolph, J. Shaughnessy, M. Gruber-Baldini, A. Alici, Y. Arora, R.C. Campbell, N. Flaherty, J. Gordon, S. Kamholz, B. Maldonado, J.R. Pandharipande, P. Parks, J. Waszynski, C. Khan, B. Neufeld, K. Olofsson, B. Thomas, C. Young, J. Davis, D. Laurila, J. Page, V. Teodorczuk, A. Agar, M. Meagher, D. Spiller, J. Schieveld, J. Milisen, K. de Rooij, S. van Munster, B. Kreisel, S. Cerejeira, J. Hasemann, W. Wilson, D. Cunningham, C. Morandi, A. Slooter, A. Detroyer, E. Caraceni, A. MacLullich, A., The DSM-5 criteria, level of arousal and delirium diagnosis: Inclusiveness is safer, BMC Medicine, 12, (1), 2014, p141-Journal Article, 2014, DOI , URL , TARA - Full Text
• Sanders, R.D. Coburn, M. Cunningham, C. Pandharipande, P., Risk factors for postoperative delirium, The Lancet Psychiatry, 1, (6), 2014, p404 - 406Journal Article, 2014, DOI , URL
• Cape, E. Hall, R.J. van Munster, B.C. de Vries, A. Howie, S.E.M. Pearson, A. Middleton, S.D. Gillies, F. Armstrong, I.R. White, T.O. Cunningham, C. de Rooij, S.E. MacLullich, A.M.J., Cerebrospinal fluid markers of neuroinflammation in delirium: A role for interleukin-1ß in delirium after hip fracture, Journal of Psychosomatic Research, 77, (3), 2014, p219 - 225Journal Article, 2014, DOI , URL , TARA - Full Text
• Delinquency in, Irish Families Under Stress Volume 3, Dublin, Ireland, E.H.B.: Dublin, 1991, pp166 - 184, [Fitzgerald M. ]Book Chapter, 1991
• Murray, C., Griffin, E.W., O'Loughlin, E., (...), Harkin, A., Cunningham, C., Interdependent and independent roles of type I interferons and IL-6 in innate immune, neuroinflammatory and sickness behaviour responses to systemic poly I: C, Brain, Behavior, and Immunity, 48, 2015, 274-286Journal Article, 2015, TARA - Full Text
• Hennessy, E; Griffin E; Cunningham C, Astrocytes are primed by chronic neurodegeneration to produce exaggerated chemokine and cell infiltration responses to acute stimulation with the cytokines IL-1β and TNF-α, Journal of Neuroscience, 35, (22), 2015, p8411 - 8422Journal Article, 2015, URL
• Renata Reis, Edel Hennessy, Caoimhe Murray, Éadaoin W. Griffin and Colm Cunningham, At the centre of neuronal, synaptic and axonal pathology in murine prion disease: degeneration of neuroanatomically linked thalamic and brainstem nuclei. , Neuropathology and Applied Neurobiology, 41 , (6), 2015, p780 - 797Journal Article, 2015, DOI
• Carroll, E.C., Jin, L., Mori, A., Muñoz-Wolf, N., Oleszycka, E., Moran, H.B.T., Mansouri, S., McEntee, C.P., Lambe, E., Agger, E.M., Andersen, P., Cunningham, C., Hertzog, P., Fitzgerald, K.A., Bowie, A.G., Lavelle, E.C., The Vaccine Adjuvant Chitosan Promotes Cellular Immunity via DNA Sensor cGAS-STING-Dependent Induction of Type I Interferons, Immunity, 44, (3), 2016, p597 - 608Journal Article, 2016, DOI
• Hennessy E, Gormley S, Lopez-Rodriguez A.B, Murray C, Murray C, Cunningham C, Systemic TNF-α produces acute cognitive dysfunction and exaggerated sickness behavior when superimposed upon progressive neurodegeneration, Brain, Behavior, and Immunity, 59, 2017, p233 - 244Journal Article, 2017, DOI , URL
• Varghese S, Cotter M, Chevot F, Fergus C, Cunningham C, Mills KH, Connon SJ, Southern JM, Kelly VP., In vivo modification of tRNA with an artificial nucleobase leads to full disease remission in an animal model of multiple sclerosis., Nucleic Acids Research, 45, (4), 2017, p2029-2039Journal Article, 2017, DOI
• Davis DH, Muniz-Terrera G, Keage HA, Stephan BC, Fleming J, Ince PG, Matthews FE, Cunningham C, Ely EW, MacLullich AM, Brayne C, Epidemiological Clinicopathological Studies in Europe (EClipSE) Collaborative Members., Association of Delirium With Cognitive Decline in Late Life: A Neuropathologic Study of 3 Population-Based Cohort Studies., JAMA Psychiatry, 74, (3), 2017, p244-251Journal Article, 2017, DOI
• AGS/NIA Delirium Conference Writing Group, Planning Committee and Faculty., The American Geriatrics Society/National Institute on Aging Bedside-to-Bench Conference: Research Agenda on Delirium in Older Adults., Journal of the American Geriatrics Society, 63, (5), 2015, p843-852Journal Article, 2015, DOI
• Immune Stimulation and Cognitive Function: Defining the Deficits and Avoiding the Pitfalls in, editor(s)Kusnecov and Anisman , Psychoneuroimmunology, Oxford, UK, 2014, pp347--364 , [Colm Cunningham]Book Chapter, 2014
• Experimental models of cognitive dysfunction in infection and critical illness in, editor(s)Stevens, Sharshar and Ely , Brain Disorders in Critical Illness, Cambridge, 2013, pp97 - 107, [Colm Cunningham, Robert D. Stevens, Tarek Sharshar, E. Wesley Ely]Book Chapter, 2013
• Viana, L.C., Lima, C.M., Oliveira, M.A., Borges, R.P., Cardoso, T.T., Almeida, I.N.F., Diniz, D.G., Bento-Torres, J., Pereira, A., Batista-de-Oliveira, M., Lopes, A.A.C., Silva, R.F.M., Abadie-Guedes, R., Amâncio dos Santos, A., Lima, D.S.C., Vasconcelos, P.F.C., Cunningham, C., Guedes, R.C.A., Picanço-Diniz, C.W., Litter size, age-related memory impairments, and microglial changes in rat dentate gyrus: Stereological analysis and three dimensional morphometry, 238, 2013, p280-296Journal Article, 2013
• Teeling, J.L., Felton, L.M., Deacon, R.M.J., Cunningham, C., Rawlins, J.N.P., Perry, V.H., Sub-pyrogenic systemic inflammation impacts on brain and behavior, independent of cytokines, 21, (6), 2007, p836-850Journal Article, 2007
• Mamad, O. and Islam, M.N. and Cunningham, C. and Tsanov, M., Differential response of hippocampal and prefrontal oscillations to systemic LPS application, Brain Research, 1681, 2018, p64-74Journal Article, 2018, DOI , URL , TARA - Full Text
• Rolandi, E. and Cavedo, E. and Pievani, M. and Galluzzi, S. and Ribaldi, F. and Buckley, C. and Cunningham, C. and Guerra, U.P. and Musarra, M. and Morzenti, S. and Magnaldi, S. and Patassini, M. and Terragnoli, F. and Matascioli, L. and Franzoni, S. and Annoni, G. and Carnevali, L. and Bellelli, G. and Frisoni, G.B., Association of postoperative delirium with markers of neurodegeneration and brain amyloidosis: a pilot study, Neurobiology of Aging, 61, 2018, p93-101Journal Article, 2018, DOI , URL
• Pandharipande, P.P. and Ely, E.W. and Arora, R.C. and Balas, M.C. and Boustani, M.A. and La Calle, G.H. and Cunningham, C. and Devlin, J.W. and Elefante, J. and Han, J.H. and MacLullich, A.M. and Maldonado, J.R. and Morandi, A. and Needham, D.M. and Page, V.J. and Rose, L. and Salluh, J.I.F. and Sharshar, T. and Shehabi, Y. and Skrobik, Y. and Slooter, A.J.C. and Smith, H.A.B., The intensive care delirium research agenda: a multinational, interprofessional perspective, Intensive Care Medicine, 43, (9), 2017, p1329-1339Journal Article, 2017, DOI , URL
• Nazmi, A., Field, R.H., Griffin, E.W., Haugh, O., Hennessy, E., Cox, D., Reis, R., Tortorelli, L., Murray, C.L., Lopez-Rodriguez, A.B., Lavelle, E.C., Dunne, A. and Cunningham,C. , Chronic neurodegeneration induces Type I interferon synthesis via STING, shaping microglial phenotype and accelerating disease progression, Glia, 67, 2019, p1254 - 1276Journal Article, 2019, DOI , TARA - Full Text
• Cunningham, C. and Dunne, A. and Lopez-Rodriguez, A.B., Astrocytes: Heterogeneous and Dynamic Phenotypes in Neurodegeneration and Innate Immunity, Neuroscientist, 2019, p455-474Journal Article, 2019, DOI , URL , TARA - Full Text
• Skelly D.T, Griffin à .W, Murray C.L, Harney S, O†Boyle C, Hennessy E, Dansereau M.-A, Nazmi A, Tortorelli L, Rawlins J.N, Bannerman D.M, Cunningham C, Correction: Acute transient cognitive dysfunction and acute brain injury induced by systemic inflammation occur by dissociable IL-1-dependent mechanisms (Molecular Psychiatry, (2018), 10.1038/s41380-018-0075-8), Molecular Psychiatry, 2019Journal Article, 2019, DOI , URL
• Hayden K.M, Inouye S.K, Cunningham C, Jones R.N, Avidan M.S, Davis D, Kuchel G.A, Tang Y, Khachaturian A.S, Reduce the burden of dementia now, Alzheimer's and Dementia, 14, (7), 2018, p845 - 847Journal Article, 2018, DOI , URL
• Arora R.C, Cunningham C, Losing sleep over delirium, Critical Care Medicine, 46, (6), 2018, p1036 - 1038Journal Article, 2018, DOI , URL
• Skelly, D.T., Griffin, É.W., Murray, C.L., (...), Bannerman, D.M., Cunningham, C. , Acute transient cognitive dysfunction and acute brain injury induced by systemic inflammation occur by dissociable IL-1-dependent mechanisms, Molecular Psychiatry, 2018, p1-Journal Article, 2018, DOI , TARA - Full Text
• Neher J.J, Cunningham C, Priming Microglia for Innate Immune Memory in the Brain, Trends in Immunology, 40, (4), 2019, p358 - 374Journal Article, 2019, DOI , URL
• Wilson, J.E. and Mart, M.F. and Cunningham, C. and Shehabi, Y. and Girard, T.D. and MacLullich, A.M.J. and Slooter, A.J.C. and Ely, E.W., Publisher Correction: Delirium (Nature Reviews Disease Primers, (2020), 6, 1, (90), 10.1038/s41572-020-00223-4), Nature Reviews Disease Primers, 6, (1), 2020Journal Article, 2020, DOI , URL , TARA - Full Text
• Oldham, M.A. and Slooter, A.J.C. and Cunningham, C. and Rahman, S. and Davis, D. and Vardy, E.R.L.C. and Garcez, F.B. and Neufeld, K.J. and de Castro, R.E.V. and Ely, E.W. and MacLullich, A., Characterising neuropsychiatric disorders in patients with COVID-19, The Lancet Psychiatry, 7, (11), 2020, p932-933Journal Article, 2020, DOI , URL , TARA - Full Text
• Oh, E.S. and Akeju, O. and Avidan, M.S. and Cunningham, C. and Hayden, K.M. and Jones, R.N. and Khachaturian, A.S. and Khan, B.A. and Marcantonio, E.R. and Needham, D.M. and Neufeld, K.J. and Rose, L. and Spence, J. and Tieges, Z. and Vlisides, P. and Inouye, S.K., A roadmap to advance delirium research: Recommendations from the NIDUS Scientific Think Tank, Alzheimer's and Dementia, 16, (5), 2020, p726-733Journal Article, 2020, DOI , URL , TARA - Full Text
• Khachaturian, A.S. and Hayden, K.M. and Devlin, J.W. and Fleisher, L.A. and Lock, S.L. and Cunningham, C. and Oh, E.S. and Fong, T.G. and Fick, D.M. and Marcantonio, E.R. and Iyengar, V. and Rockwood, K. and Kuchel, G.A. and Eckenhoff, R.G. and MacLullich, A.M.J. and Jones, R.N. and Davis, D. and D'Antonio, P.M. and Fargo, K.N. and Albert, M.S. and Williamson, J.D. and Ling, S.M. and Weiss, J. and Karlawish, J. and Petersen, R.C. and Blazer, D.G. and Khachaturian, Z.S. and Inouye, S.K., International drive to illuminate delirium: A developing public health blueprint for action, Alzheimer's and Dementia, 16, (5), 2020, p711-725Journal Article, 2020, DOI , URL , TARA - Full Text
• Skelly, D.T. and Griffin, à .W. and Murray, C.L. and Harney, S. and O†Boyle, C. and Hennessy, E. and Dansereau, M.-A. and Nazmi, A. and Tortorelli, L. and Rawlins, J.N. and Bannerman, D.M. and Cunningham, C., Correction: Acute transient cognitive dysfunction and acute brain injury induced by systemic inflammation occur by dissociable IL-1-dependent mechanisms (Molecular Psychiatry, (2019), 24, 10, (1533-1548), 10.1038/s41380-018-0075-8), Molecular Psychiatry, 24, (10), 2019, p1566Journal Article, 2019, DOI , URL
• Leavey, N. and Hammond, S.P. and Shepstone, L. and Cross, J. and Zetterberg, H. and Cunningham, C. and MacLullich, A. and Leiv Otto Watne and Minihane, A.M. and Ballard, C. and Knapskog, A.-B. and Hall, R. and Howard, G. and Hammond, M. and Fox, C., Study protocol: ASCRIBED: the impact of Acute SystematiC inflammation upon cerebRospinal fluId and blood BiomarkErs of brain inflammation and injury in dementia: A study in acute hip fracture patients, BMC Neurology, 19, (1), 2019Journal Article, 2019, DOI , URL
• Torvell, M. and Hampton, D.W. and Connick, P. and MacLullich, A.M.J. and Cunningham, C. and Chandran, S., A single systemic inflammatory insult causes acute motor deficits and accelerates disease progression in a mouse model of human tauopathy, Alzheimer's and Dementia: Translational Research and Clinical Interventions, 5, 2019, p579-591Journal Article, 2019, DOI , URL
• Wilson, J.E., Mart, M.F., Cunningham, C. et al., Delirium, Nat Rev Dis Primers , 6, (90), 2020Journal Article, 2020, DOI , TARA - Full Text
• Kealy, Acute Inflammation Alters Brain Energy Metabolism in Mice and Humans: Role in Suppressed Spontaneous Activity, Impaired Cognition, and Delirium, Journal of Neuroscience, 2020, p10.1523/JNEUROSCI.2876-19.2020Journal Article, 2020, TARA - Full Text
• Hough, K. and Verschuur, C.A. and Cunningham, C. and Newman, T.A., Macrophages in the cochlea; an immunological link between risk factors and progressive hearing loss, GLIA, 70, (2), 2022, p219-238Journal Article, 2022, DOI , URL , TARA - Full Text
• Lopez-Rodriguez, A.B. and Hennessy, E. and Murray, C.L. and Nazmi, A. and Delaney, H.J. and Healy, D. and Fagan, S.G. and Rooney, M. and Stewart, E. and Lewis, A. and de Barra, N. and Scarry, P. and Riggs-Miller, L. and Boche, D. and Cunningham, M.O. and Cunningham, C., Acute systemic inflammation exacerbates neuroinflammation in Alzheimer's disease: IL-1β drives amplified responses in primed astrocytes and neuronal network dysfunction, Alzheimer's and Dementia, 17, (10), 2021, p1735-1755Journal Article, 2021, DOI , URL , TARA - Full Text
• McGarry, N. and Murray, C.L. and Garvey, S. and Wilkinson, A. and Tortorelli, L. and Ryan, L. and Hayden, L. and Healy, D. and Griffin, E.W. and Hennessy, E. and Arumugam, M. and Skelly, D.T. and Mitchell, K.J. and Cunningham, C., Double stranded RNA drives anti-viral innate immune responses, sickness behavior and cognitive dysfunction dependent on dsRNA length, IFNAR1 expression and age, Brain, Behavior, and Immunity, 95, 2021, p413-428Journal Article, 2021, DOI , URL , TARA - Full Text
• O'Neill, E. and Griffin, Ã .W. and O'Sullivan, R. and Murray, C. and Ryan, L. and Yssel, J. and Harkin, A. and Cunningham, C., Acute neuroinflammation, sickness behavior and working memory responses to acute systemic LPS challenge following noradrenergic lesion in mice, Brain, Behavior, and Immunity, 94, 2021, p357-368Journal Article, 2021, DOI , TARA - Full Text
• Escartin, C. and Galea, E. and Lakatos, A. and O†Callaghan, J.P. and Petzold, G.C. and Serrano-Pozo, A. and SteinhÀuser, C. and Volterra, A. and Carmignoto, G. and Agarwal, A. and Allen, N.J. and Araque, A. and Barbeito, L. and Barzilai, A. and Bergles, D.E. and Bonvento, G. and Butt, A.M. and Chen, W.-T. and Cohen-Salmon, M. and Cunningham, C. and Deneen, B. and De Strooper, B. and Díaz-Castro, B. and Farina, C. and Freeman, M. and Gallo, V. and Goldman, J.E. and Goldman, S.A. and Götz, M. and Gutiérrez, A. and Haydon, P.G. and Heiland, D.H. and Hol, E.M. and Holt, M.G. and Iino, M. and Kastanenka, K.V. and Kettenmann, H. and Khakh, B.S. and Koizumi, S. and Lee, C.J. and Liddelow, S.A. and MacVicar, B.A. and Magistretti, P. and Messing, A. and Mishra, A. and Molofsky, A.V. and Murai, K.K. and Norris, C.M. and Okada, S. and Oliet, S.H.R. and Oliveira, J.F. and Panatier, A. and Parpura, V. and Pekna, M. and Pekny, M. and Pellerin, L. and Perea, G. and Pérez-Nievas, B.G. and Pfrieger, F.W. and Poskanzer, K.E. and Quintana, F.J. and Ransohoff, R.M. and Riquelme-Perez, M. and Robel, S. and Rose, C.R. and Rothstein, J.D. and Rouach, N. and Rowitch, D.H. and Semyanov, A. and Sirko, S. and Sontheimer, H. and Swanson, R.A. and Vitorica, J. and Wanner, I.-B. and Wood, L.B. and Wu, J. and Zheng, B. and Zimmer, E.R. and Zorec, R. and Sofroniew, M.V. and Verkhratsky, A., Reactive astrocyte nomenclature, definitions, and future directions, Nature Neuroscience, 24, (3), 2021, p312-325Journal Article, 2021, DOI , URL , TARA - Full Text
• Tsui, A. and Searle, S.D. and Bowden, H. and Hoffmann, K. and Hornby, J. and Goslett, A. and Weston-Clarke, M. and Hamill Howes, L. and Street, R. and Perera, R. and Taee, K. and Kustermann, C. and Chitalu, P. and Razavi, B. and Magni, F. and Das, D. and Kim, S. and Chaturvedi, N. and Sampson, E.L. and Rockwood, K. and Cunningham, C. and Ely, E.W. and Richardson, S.J. and Brayne, C. and Muniz Terrera, G. and Tieges, Z. and MacLullich, A. and Davis, D., The effect of baseline cognition and delirium on long-term cognitive impairment and mortality: a prospective population-based study, The Lancet Healthy Longevity, 3, (4), 2022, pe232-e241Journal Article, 2022, DOI , URL
• Eckenhoff, M.F. and Cunningham, C., Animal Models and Cognitive Testing of Perioperative Neurocognitive Disorders, 2019, 61-81ppBook, 2019, DOI , URL
• Paolicelli, R.C. and Sierra, A. and Stevens, B. and Tremblay, M.-E. and Aguzzi, A. and Ajami, B. and Amit, I. and Audinat, E. and Bechmann, I. and Bennett, M. and Bennett, F. and Bessis, A. and Biber, K. and Bilbo, S. and Blurton-Jones, M. and Boddeke, E. and Brites, D. and BrÃŽne, B. and Brown, G.C. and Butovsky, O. and Carson, M.J. and Castellano, B. and Colonna, M. and Cowley, S.A. and Cunningham, C. and Davalos, D. and De Jager, P.L. and de Strooper, B. and Denes, A. and Eggen, B.J.L. and Eyo, U. and Galea, E. and Garel, S. and Ginhoux, F. and Glass, C.K. and Gokce, O. and Gomez-Nicola, D. and González, B. and Gordon, S. and Graeber, M.B. and Greenhalgh, A.D. and Gressens, P. and Greter, M. and Gutmann, D.H. and Haass, C. and Heneka, M.T. and Heppner, F.L. and Hong, S. and Hume, D.A. and Jung, S. and Kettenmann, H. and Kipnis, J. and Koyama, R. and Lemke, G. and Lynch, M. and Majewska, A. and Malcangio, M. and Malm, T. and Mancuso, R. and Masuda, T. and Matteoli, M. and McColl, B.W. and Miron, V.E. and Molofsky, A.V. and Monje, M. and Mracsko, E. and Nadjar, A. and Neher, J.J. and Neniskyte, U. and Neumann, H. and Noda, M. and Peng, B. and Peri, F. and Perry, V.H. and Popovich, P.G. and Pridans, C. and Priller, J. and Prinz, M. and Ragozzino, D. and Ransohoff, R.M. and Salter, M.W. and Schaefer, A. and Schafer, D.P. and Schwartz, M. and Simons, M. and Smith, C.J. and Streit, W.J. and Tay, T.L. and Tsai, L.-H. and Verkhratsky, A. and von Bernhardi, R. and Wake, H. and Wittamer, V. and Wolf, S.A. and Wu, L.-J. and Wyss-Coray, T., Microglia states and nomenclature: A field at its crossroads, Neuron, 110, (21), 2022, p3458-3483Journal Article, 2022, DOI , URL
• Yin Yang, Tomas Ondrejcak, Neng-Wei Hu, Sadia Islam, Eugene O'Rourke, Richard Reilly, Colm Cunningham, Michael Rowan, Igor Klyubin, Gamma-patterned sensory stimulation reverses synaptic plasticity deficits in rat models of early Alzheimer's disease, European Journal of Neuroscience, 58, (6), 2023, p3402 - 3411Journal Article, 2023, DOI
• Tsui, A. and Yeo, N. and Searle, S.D. and Bowden, H. and Hoffmann, K. and Hornby, J. and Goslett, A. and Weston-Clarke, M. and Lanham, D. and Hogan, P. and Seeley, A. and Rawle, M. and Chaturvedi, N. and Sampson, E.L. and Rockwood, K. and Cunningham, C. and Wesley Ely, E. and Richardson, S.J. and Brayne, C. and Terrera, G.M. and Tieges, Z. and MacLullich, A.M.J. and Davis, D., Extremes of baseline cognitive function determine the severity of delirium: a population study, Brain, 146, (5), 2023, p2132-2141Journal Article, 2023, DOI , URL
• Vasunilashorn, S.M. and Lunardi, N. and Newman, J.C. and Crosby, G. and Acker, L. and Abel, T. and Bhatnagar, S. and Cunningham, C. and de Cabo, R. and Dugan, L. and Hippensteel, J.A. and Ishizawa, Y. and Lahiri, S. and Marcantonio, E.R. and Xie, Z. and Inouye, S.K. and Terrando, N. and Eckenhoff, R.G., Preclinical and translational models for delirium: Recommendations for future research from the NIDUS delirium network, Alzheimer's and Dementia, 19, (5), 2023, p2150-2174Journal Article, 2023, DOI , URL
• Bowman, E.M.L. and Brummel, N.E. and Caplan, G.A. and Cunningham, C. and Evered, L.A. and Fiest, K.M. and Girard, T.D. and Jackson, T.A. and LaHue, S.C. and Lindroth, H.L. and Maclullich, A.M.J. and McAuley, D.F. and Oh, E.S. and Oldham, M.A. and Page, V.J. and Pandharipande, P.P. and Potter, K.M. and Sinha, P. and Slooter, A.J.C. and Sweeney, A.M. and Tieges, Z. and Van Dellen, E. and Wilcox, M.E. and Zetterberg, H. and Cunningham, E.L., Advancing specificity in delirium: The delirium subtyping initiative, Alzheimer's and Dementia, 2023Journal Article, 2023, DOI , URL
• Healy, D. and Murray, C. and McAdams, C. and Power, R. and Hollier, P.-L. and Lambe, J. and Tortorelli, L. and Lopez-Rodriguez, A.B. and Cunningham, C., Susceptibility to acute cognitive dysfunction in aged mice is underpinned by reduced white matter integrity and microgliosis, Communications Biology, 7, (1), 2024Journal Article, 2024, DOI , URL
• Sanders, R.D. and Watne, L. and Roberson, S.W. and Kimchi, E.Y. and Slooter, A.J.C. and Cunningham, C. and Nourski, K.V. and Palanca, B.J.A. and Lennertz, R. and Banks, M.I., International Delirium Pathophysiology & Electrophysiology Network for Data sharing (iDEPEND), BJA Open, 11, (100304), 2024Journal Article, 2024, DOI , URL
• Aldecoa, C. and Bettelli, G. and Bilotta, F. and Sanders, R.D. and Aceto, P. and Audisio, R. and Cherubini, A. and Cunningham, C. and Dabrowski, W. and Forookhi, A. and Gitti, N. and Immonen, K. and Kehlet, H. and Koch, S. and Kotfis, K. and Latronico, N. and MacLullich, A.M.J. and Mevorach, L. and Mueller, A. and Neuner, B. and Piva, S. and Radtke, F. and Blaser, A.R. and Renzi, S. and Romagnoli, S. and Schubert, M. and Slooter, A.J.C. and Tommasino, C. and Vasiljewa, L. and Weiss, B. and Yuerek, F. and Spies, C.D., Update of the European Society of Anaesthesiology and Intensive Care Medicine evidence-based and consensus-based guideline on postoperative delirium in adult patients, European Journal of Anaesthesiology, 41, (2), 2024, p81-108Journal Article, 2024, DOI , URL
• Titlestad, I. and Watne, L.O. and Caplan, G.A. and McCann, A. and Ueland, P.M. and Neerland, B.E. and Myrstad, M. and Halaas, N.B. and Pollmann, C.T. and Henjum, K. and Ranhoff, A.H. and Solberg, L.B. and Figved, W. and Cunningham, C. and Giil, L.M., Impaired glucose utilization in the brain of patients with delirium following hip fracture, Brain, 147, (1), 2024, p215-223Journal Article, 2024, DOI , URL
• Lopez-Rodriguez, A.B. and Murray, C.L. and Kealy, J. and Towns, C. and Roche, A. and Nazmi, A. and Doran, M. and Lowry, J.P. and Cunningham, C., Hyperthermia elevates brain temperature and improves behavioural signs in animal models of autism spectrum disorder, Molecular Autism, 14, (1), 2023Journal Article, 2023, DOI , URL
• Neuner, B. and Wolter, S. and Mccarthy, W.J. and Spies, C. and Cunningham, C. and Radtke, F.M. and Franck, M. and Koenig, T., EEG microstate quantifiers and state space descriptors during anaesthesia in patients with postoperative delirium: a descriptive analysis, Brain Communications, 5, (6), 2023Journal Article, 2023, DOI , URL
• Mouse behavioural studies and what they can teach us about prion diseases in, editor(s)David Brown , Neurodegeneration and prion disease, New York, Springer, 2005, pp111 - 137, [Colm Cunningham]Book Chapter, 2005, DOI
• Perry V.H., Newman, T.A. Cunningham, C, The impact of systemic infection on neurodegenerative disease, Nature reviews Neuroscience, 4, (February), 2003, p103 - 112Journal Article, 2003, DOI
• Perry, V.H., Cunningham, C. and Boche, Atypical inflammation in the central nervous system in prion disease, Current Opinion in Neurology , 15, 2002, p349-354Journal Article, 2002, DOI
• Delphine Boche, Colm Cunningham*, Fabian Docagne, Helen Scott and V. Hugh Perry , TGFb1 regulates the inflammatory response during chronic neurodegeneration , Neurobiology of Disease, 22, ((3)), 2006, p638-650Journal Article, 2006, DOI
• Colm Cunningham, Suzanne Campion, Jessica Teeling, Leigh Felton and V.H.Perry, The sickness behaviour and CNS inflammatory mediator profile induced by systemic challenge of mice with synthetic double stranded RNA (Poly I:C)., Brain, Behavior and Immunity, 21, (4), 2007, p490 - 502Journal Article, 2007, DOI
• Cunningham, C., Wilcockson D.C., Campion, S., Lunnon K. and Perry, V.H. , Central and systemic endotoxin challenges exacerbate the local inflammatory response and increase neuronal death during chronic neurodegeneration, Journal of Neuroscience, 25, ((40)), 2005, p9275-9284Journal Article, 2005, DOI
• Felton, L., Cunningham, C. Rankine, E., Waters, S. and V. Hugh Perry, The role of monocyte chemoattractant protein-1 (MCP-1) in murine prion disease: separation of early behavioural dysfunction from overt clinical disease, Neurobiology of Disease, 20, (2), 2005, p283-295Journal Article, 2005, DOI
• Cunningham C., Wilcockson, D.C., Boche, D. and Perry, V.H., A comparison of brain and peripheral organ cytokine and acute phase protein transcription in the ME7 model of prion disease, Journal of Virology, 79, (8), 2005, p5174-5184Journal Article, 2005
• Cunningham, C., Deacon, R.M.J., Chan, K., Boche, D., Rawlins, J.N.P. and Perry, V.H. , Neuropathologically distinct prion disease strains give rise to similar behavioural profiles, Neurobiology of Disease, 18, 2005, p258-269Journal Article, 2005, DOI
• Picanco-Diniz, C.W., Boche, D., Gomes-Leal, W., Perry, V.H. and Cunningham, C., Neuropil and Neuronal changes in hippocampal NADPH-diaphorase histochemistry in the ME7 model of murine prion disease, Neuropathology and Applied Neurobiology, 30, 2004, p292-303Journal Article, 2004, DOI
• Boche, D., Cunningham, C., Gauldie, J. and Perry, V.H., Transforming Growth Factor-b1-mediated Neuroprotection Against Excitotoxic injury in Vivo, Journal of Cerebral Blood Flow and Metabolism, 23, 2003, p1174-1182Journal Article, 2003, DOI
• Cunningham, C., Deacon, R.M.J., Wells, H., Boche, D., Waters, S., Picano Diniz, C., Scott, H., Rawlins, J.N.P. and Perry V.H., Synaptic changes characterise early behavioural signs in the ME7 model of murine prion disease, European Journal of Neuroscience , 17, 2003, p2147-2155Journal Article, 2003, DOI
• Holmes, C., El-Oki, M., Williams, A.L., Cunningham, C., Wilcockson, D. and Perry, V.H. , Systemic infection, interleukin-1b and cognitive decline in Alzheimer's disease., Journal of Neurology Neurosurgery and Psychiatry , 74, 2003, p788-789.Journal Article, 2003
• Combrinck, M.I., Perry, V.H. and Cunningham C., Peripheral infection evokes exaggerated sickness behaviour in pre-clinical murine prion disease, Neuroscience., 112, 2002, p7-11Journal Article, 2002, DOI
• Cunningham, C., Boche, D. and Perry, V.H., Transforming growth factor b1, the dominant cytokine in murine prion disease: influence on inflammatory cytokine synthesis and alteration of vascular extracellular matrix. , Neuropath Appl. Neurobiol. , 28, 2002, p107-119Journal Article, 2002
• Minghetti, L., Greco, A., Cardone, F., Puopolo, M., Ladogana, A., Almonti, S., Cunningham, C., Perry, V. H., Pocchiari, M. and Levi, G., ncreased brain synthesis of prostaglandin E2 and F2-isoprostane in human and experimental transmissible spongiform encephalopathies, Journal of Neuropathology and Experimental Neurology, 59, ((10)), 2000, p866-871Journal Article, 2000
• Bartolini B, Tipton KF, Bianchi L, Stephenson D, Cunningham C, Della Corte L., Determination of monoamine oxidase activity by HPLC with fluorimetric detection, Neurobiology (Bp), 79, ((2)), 1999, p109-21Journal Article, 1999
• Colm Cunningham, Keith F. Tipton and Henry B.F. Dixon, Conversion of taurine into N-chlorotaurine (taurine chloramine) and sulphoacetaldehyde in response to oxidative stress, Biochemical Journal, 330, 1998, p939-945.Journal Article, 1998
• Perry, V.H., Cunningham, C. and Holmes, C, Systemic infections affect chronic neurodegeneration, Nature Reviews Immunology, 7, (2), 2007, p161 - 167Journal Article, 2007, DOI
• Cunningham, C., Campion, S., Lunnon, K., Deacon, R.M.J, Rawlins, J.N.P. and Perry, V.H., Systemic inflammation superimposed on chronic neurodegeneration induces acute behavioural and cognitive changes and accelerates neurological decline. , Biological Psychiatry , 65, (4), 2009, p305 - 312Journal Article, 2009, DOI
• Cunningham, C and Sanderson, D., Malaise in the water Maze: untangling the effects of IL-1b and LPS on learning and memory, Brain Behavior and Immunity, 22, (8), 2008, p1117 - 1127Journal Article, 2008, DOI
• Alasdair MacLullich, Sophia de Rooij, Thomas Miller, Karen Ferguson and Colm Cunningham. , Unravelling the pathophysiology of delirium: a focus on aberrant stress responses. , Journal of Psychosomatic Research, 65, (3), 2008, p229 - 238Journal Article, 2008, DOI
• Ayodeji A Asuni, Colm Cunningham, Piranvhan Vigneswaran, Hugh V Perry and Vincent O'Connor. , Unaltered SNARE complex formation in an in vivo model of Prion disease, Brain Research, 1233, 2008, p1 - 7Journal Article, 2008, DOI
• Palin, P., Cunningham, C., Forse, P., V. Hugh Perry and Nick Platt., Systemic inflammation switches the inflammatory cytokine profile in CNS Wallerian degeneration, Neurobiology of Disease, 30, 2008, p19 - 29Journal Article, 2008, DOI
• David J. Sanderson, Colm Cunningham, Robert, M.J. Deacon, David, M. Bannerman, V. Hugh Perry, & J. Nicholas P. Rawlins., A double dissociation between the effects of sub-pyrogenic systemic inflammation and hippocampal lesions on learning, Behavioural Brain Research, 201, (1), 2009, p103 - 111Journal Article, 2009, DOI
• Orla Cunningham, Suzanne Campion, V Hugh Perry, Nicolai Sidenius, Fabian Docagne and Colm Cunningham, Microglia and the urokinase plasminogen activator receptor (uPAR) / uPA system in innate brain inflammation, GLIA, 57, (16), 2009, p1802 - 1814Journal Article, 2009, DOI
• Clive Holmes, Colm Cunningham, Elina Zotova, Jan Woolford, Christine Dean, Sara Kerr, David Culliford, and Hugh Perry, Systemic inflammation and disease progression in Alzheimer's disease, Neurology, 73, (10), 2009, p768 - 774Journal Article, 2009, DOI
• J.L. Teeling, C. Cunningham. T.A. Newman and V.H. Perry, The effect of non-steroidal anti-inflammatory agents on behavioural changes and cytokine production following systemic inflammation: Implications for a role of COX-1, Brain, Behavior and Immunity, 24, (3), 2010, p409-19Journal Article, 2010, DOI
• Martina M. Hughes, Robert H. Field, V. Hugh Perry, Carol L Murray and Colm Cunningham. , Microglia in the degenerating brain are capable of phagocytosis of beads and of apoptotic cells, but do not efficiently remove PrPSc, even upon LPS stimulation , GLIA, 58, 2010, p2017 - 2030Journal Article, 2010, DOI
• Carol Murray, David Sanderson, Chris Barkus, R.M.J. Deacon, J.N.P. Rawlins, David Bannerman and Colm Cunningham, Systemic inflammation induces acute working memory deficits in the primed brain; relevance for delirium, Neurobiology of Aging, 33, (3), 2012, p603-616.e3Journal Article, 2012, DOI , URL , TARA - Full Text
• Robert Field, Suzanne Campion, Colleen Warren, Carol Murray and Colm Cunningham, Activation of the systemic anti-viral response by poly I:C exacerbates chronic neurodegeneration: microglial priming and amplified IFNβ and IL-1β responses , Brain Behavior and Immunity , 24, (6), 2010, p996-1007Journal Article, 2010
• Aline Andrade de Sousa, Renata Reis, João Bento-Torres, Nonata Trévia, Nara Alves de Almeida Lins, Aline Passos, Zaire Santos, José Antonio Picanço Diniz, Pedro Fernando da Costa Vasconcelos, Colm Cunningham, Victor Hugh Perry, Cristovam Wanderley Picanço Diniz, Influence of Enriched Environment on Viral Encephalitis Outcomes: Behavioral and Neuropathological Changes in Albino Swiss Mice, PLoS ONE, 6, (1, e15597), 2011Journal Article, 2011, DOI , URL , TARA - Full Text
• Carol L Murray, Donal T Skelly and Colm Cunningham, Exacerbation of CNS inflammation and neurodegeneration by systemic LPS treatment is independent of circulating IL-1 beta and IL-6, JOURNAL OF NEUROINFLAMMATION, 8, (50), 2011Journal Article, 2011, DOI , URL , TARA - Full Text
• Colm Cunningham, Systemic inflammation and delirium: important co-factors in the progression of dementia, Biochemical Society Transactions, 39, 2011, p945 - 953Review Article, 2011, DOI , TARA - Full Text
• Cunningham C, Skelly DT, Non-Steroidal Anti-Inflammatory Drugs and Cognitive Function: Are Prostaglandins at the Heart of Cognitive Impairment in Dementia and Delirium ?, Journal of Neuroimmune Pharmacology : The Official Journal of the Society on NeuroImmune Pharmacology, 7, (1), 2012, p60-73Journal Article, 2012, DOI , URL , TARA - Full Text
• Holmes C, Cunningham C, Zotova E, Culliford D, Perry VH., Proinflammatory cytokines, sickness behavior, and Alzheimer disease., Neurology, 77, (3), 2011, p212 - 218Journal Article, 2011, DOI , URL
• Field RH, Gossen A, Cunningham C, Prior pathology in the basal forebrain cholinergic system predisposes to inflammation-induced working memory deficits: reconciling inflammatory and cholinergic hypotheses of delirium., The Journal of Neuroscience, 32, (18), 2012, p6288 - 6294Journal Article, 2012, DOI , URL , TARA - Full Text
• Cunningham C, MacLullich AM, At the extreme end of the psychoneuroimmunological spectrum: delirium as a maladaptive sickness behaviour response, Brain, Behavior and Immunity, 28, 2013, p1 - 13Journal Article, 2013, URL , TARA - Full Text
• Cunningham C, Microglia and neurodegeneration: The role of systemic inflammation, GLIA, 61, 2013, p71 - 90Journal Article, 2013, URL
• Sanderson DJ, Rawlins JN, Deacon RM, Cunningham C, Barkus C, Bannerman DM., Hippocampal lesions can enhance discrimination learning despite normal sensitivity to interference from incidental information., Hippocampus, 22, (7), 2012, p1553 - 1566Journal Article, 2012, DOI
• Borner R, Bento-Torres J, Souza DR, Sadala DB, Trevia N, Farias JA, Lins N, Passos A, Quintairos A, Diniz JA, Perry VH, Vasconcelos PF, Cunningham C, Picanço-Diniz CW. , Early behavioral changes and quantitative analysis of neuropathological features in murine prion disease: Stereological analysis in the albino Swiss mice model., Prion, 5, (3), 2011, 215-227Journal Article, 2011
• Skelly DT, Hennessy E, Dansereau MA, Cunningham C, A Systematic Analysis of the Peripheral and CNS Effects of Systemic LPS, IL-1beta, TNF-alpha and IL-6 Challenges in C57BL/6 Mice., PloS one, 8, (7), 2013, pe69123Journal Article, 2013, DOI , TARA - Full Text
• Griffin EW, Skelly DT, Murray CL, Cunningham C, Cyclooxygenase-1-dependent prostaglandins mediate susceptibility to systemic inflammation-induced acute cognitive dysfunction., The Journal of neuroscience : the official journal of the Society for Neuroscience, 33, (38), 2013, p15248-58Journal Article, 2013, DOI , TARA - Full Text
• Maclullich AM, Anand A, Davis DH, Jackson T, Barugh AJ, Hall RJ, Ferguson KJ, Meagher DJ, Cunningham C, New horizons in the pathogenesis, assessment and management of delirium., Age and ageing, 42, (6), 2013, p667-74Journal Article, 2013, DOI , TARA - Full Text
• Davis DH, Muniz Terrera G, Keage H, Rahkonen T, Oinas M, Matthews FE, Cunningham C, Polvikoski T, Sulkava R, MacLullich AM, Brayne C, Delirium is a strong risk factor for dementia in the oldest-old: a population-based cohort study., Brain : a journal of neurology, 135, (Pt 9), 2012, p2809-16Journal Article, 2012, DOI , TARA - Full Text
• Munster BC, Aronica E, Zwinderman AH, Eikelenboom P, Cunningham C, Rooij SE, Neuroinflammation in delirium: a postmortem case-control study., Rejuvenation research, 14, (6), 2011, p615-22Journal Article, 2011, DOI
• Diniz, D.G., Foro, C.A.R., Sosthenes, M.C.K., (...), Vasconcelos, P.F.C., Diniz, C.W.P., Aging and environmental enrichment exacerbate inflammatory response on antibody-enhanced dengue disease in immunocompetent murine model, European Journal of Inflammation, 11, (3), 2013, 719-731Journal Article, 2013
• Hilton, KJ, Cunningham, C, Reynolds, RA, Perry, VH, Early Hippocampal Synaptic Loss Precedes Neuronal Loss and Associates with Early Behavioural Deficits in Three Distinct Strains of Prion Disease, PLOS ONE, 8, (6), 2013, e68062-Journal Article, 2013, DOI , TARA - Full Text
• Diniz, DG, Foro, CAR, Turiel, MCP, Sosthenes, MCK, Demachki, S, Gomes, GF, Rego, CMD, Magalhaes, MC, Pinho, BG, Ramos, JP, Casseb, SMM, Brito, MD, da Silva, EVP, Nunes, MRT, Diniz, JAP, Cunningham, C, Perry, VH, Vasconcelos, PFC, Diniz, CWP, Environmental influences on antibody-enhanced dengue disease outcomes, MEMORIAS DO INSTITUTO OSWALDO CRUZ, 107, (8), 2012, p1021-+Journal Article, 2012
• MacLullich, A.M.J., Edelshain, B.T., Hall, R.J., (...), De Rooij, S.E., Van Munster, B.C., Cerebrospinal fluid interleukin-8 levels are higher in people with hip fracture with perioperative delirium than in controls, Journal of the American Geriatrics Society, 59, (6), 2011, p1151-1153Journal Article, 2011, DOI
• Watkins, AJ, Wilkins, A, Cunningham, C, Perry, VH, Seet, MJ, Osmond, C, Eckert, JJ, Torrens, C, Cagampang, FRA, Cleal, J, Gray, WP, Hanson, MA, Fleming, TP, Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring, JOURNAL OF PHYSIOLOGY-LONDON, 586, (8), 2008, p2231-2244Journal Article, 2008, DOI
• Watkins, AJ, Ursell, E, Panton, R, Papenbrock, T, Ollis, LH, Cunningham, C, Wilkins, A, Perry, VH, Sheth, B, Kwong, WY, Eckert, JJ, Wild, AE, Hanson, MA, Osmond, C, Fleming, TP, Adaptive responses by mouse early embryos to maternal diet protect fetal growth but predispose to adult onset disease, BIOLOGY OF REPRODUCTION, 78, (2), 2008, p299-306Journal Article, 2008, DOI
• Davis DH, Skelly DT, Murray C, Hennessy E, Bowen J, Norton S, Brayne C, Rahkonen T, Sulkava R, Sanderson DJ, Rawlins JN, Bannerman DM, MacLullich AM, Cunningham C, Worsening Cognitive Impairment and Neurodegenerative Pathology Progressively Increase Risk for Delirium., The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 23, (4), 2015, 403-415Journal Article, 2015, DOI , TARA - Full Text
• Murray CL, Obiang P, Bannerman D, Cunningham C, Endogenous IL-1 in cognitive function and anxiety: a study in IL-1RI-/- mice., PloS one, 8, (10), 2013, pe78385Journal Article, 2013, DOI , TARA - Full Text

• Donal Skelly, Eadaoin W Griffin, Carol Murray, Sarah Harney, Conor O'Boyle, Edel Hennessy, Nicholas Rawlins, David Bannerman, Colm Cunningham, Acute transient cognitive dysfunction and acute brain injury induced by systemic inflammation occur by dissociable IL-1-dependent mechanisms, bioRxiv, 2017Dataset
• Colm Cunningham, American Delirium Society Annual Meeting, Nashville, June, 2016Invited Talk
• Colm Cunningham, European Delirium Association annual meeting 2017, Oslo, Autumn, 2017Invited Talk
• Colm Cunningham, Immunology research series, University of Cambridge, October, 2016Invited Talk
• Colm Cunningham, Neurosciences in Intensive Care Symposium, Pasteur institute, Paris, June, 2016Invited Talk
• Colm Cunningham, Keynote lecture, European Delirium Associaton/British Geriatric Society Meeting, London, September, 2015, BGS/EDAInvited Talk
• Colm Cunningham, British Association for Psychopharmacology Conference, Bristol, August, 2015, BAPInvited Talk
• Colm Cunningham, "Delirium in Older Adults: Finding Order in the Disorder", , NIH, Bethesda, Maryland, USA, February, 2014, National Institute of Aging & American Geriatrics SocietyInvited Talk
• Robert Dantzer(ed.), Cytokines in the ageing brain, Trends in Neurosciences, Arcachon, France, 25, ((11)), June 2002, Elsevier, 2002, 546-547 pProceedings of a Conference, DOI

• Title

  The impact of acute systemic inflammation upon CSF and blood biomarkers of brain inflammation and injury in dementia: a study in acute hip fracture and memory clinic patients
  Summary

  We propose that acute inflammatory insults, such as trauma and surgery, cause new brain injury in older adults. The current project aims to identify the inflammatory biomarkers predictive of such injury and the neuronal and synaptic biomarkers that are demonstrative of such brain injury. We aim to collect cerebrospinal fluid and blood from patients who experience hip fractures (and who have spinal anaesthesia to facilitate hip-fracture repair surgery) in order to sample the circulating and brain levels of inflammatory mediators and of markers of neuronal damage. We will then assess cognitive decline and sample blood at 1, 3 and 6 months to assess the progression of cognitive decline in those who experienced this inflammatory trauma.. We predict that the severity of acute brain inflammation and the levels of specific neuronal injury markers will predict the rate of cognitive decline in the proceeding 6 months.
  Funding Agency

  Alzheimer's Research UK
  Date From

  Nov 2016
  Date To

  Nov 2018
• Title

  Towards and understanding of infection-induced delirium
  Summary

  Delirium is a transient disorder of orientation and cognition that is highly prevalent in the elderly population admitted to or resident in hospital (10-30%). The highest risk factors for episodes of delirium are ageing and dementia and these episodes are most commonly triggered by infection, injury or surgery. Thus, while the aetiology of delirium is unknown, it is clearly multi-factorial and may result from the interaction of prior pathology and superimposed inflammatory insults. We have shown that prion-diseased mice show cognitive impairments typical of dementia and show neurodegeneration and associated CNS inflammation in neural pathways that underlie cognitive processes. These mice also show exaggerated acute sickness behaviour responses to systemic inflammatory challenges and these are underpinned by acutely raised cytokines in the hippocampus. We hypothesise that prior CNS inflammation, such as that induced by neurodegeneration, is acutely exacerbated by systemic inflammation and precipitates episodes of delirium. In the current proposal we aim to establish a mouse model of infection-induced delirium. We will investigate whether systemic inflammatory insults have more severe cognitive consequences in animals with prior CNS inflammation than in normal animals. We will investigate the cellular and molecular mechanisms of delirium using the model developed during this work.
  Funding Agency

  The Wellcome Trust
  Date From

  23/10/06
  Date To

  22/10/10
• Title

  Reconciling Cholinergic and inflammatory hypotheses of delirium: acute and lasting effects of systemic inflammation on chronic neurodegeneration
  Summary

  1) Reconciling inflammatory and cholinergic mechanisms of delirium. I propose that prior pathology in the basal forebrain cholinergic nuclei (BFCN) predisposes individuals to systemic inflammation-induced acute cognitive impairments. I will produce selective and limited lesions of the BFCN, with p75NTR-saporin that do not cause significant cognitive impairment. I predict that superimposed systemic inflammation will then induce acute cholinergic dysfunction specifically in lesioned animals. This will be a valuable model system with which to study aspects of cholinergic hypofunction-associated delirium and I will study inflammatory, behavioural and neurochemical aspects of this system. 2) Mechanisms of long-term decline. Using both the "ME7+systemic inflammation" and p75-saporin models of delirium during dementia I will study potential mechanisms of acute impairments and long-term decline resulting from inflammatory challenges. In so doing I will examine the idea that the acute cognitive dysfunction and the subsequent long-term cognitive impairment associated with delirium are two distinct processes: an acute neurochemical change and an acute pathological change that is superimposed on the existing pathological state. 3) Microglial priming. I predict that primed microglia have a role in both acute and long-term consequences of acute inflammatory episodes. I propose that priming of these CNS macrophages consists of hyper-responsiveness to a variety of inflammatory stimuli and I will investigate this with respect to receptor expression, cytosolic levels of key transcription factors and nuclear localization of these in response to inflammatory stimulation.
  Funding Agency

  Wellcome Trust
  Date From

  2010
  Date To

  2017
• Title

  Fever & the brain in autism: temperature vs. inflammatory effects
  Summary

  We will investigate the hypothesis that fever can ameliorate symptoms of autism, and explore possible mechanisms in mouse models. We will: 1) Dissociate fever and inflammation (i.e. induce whole body hyperthermia in the absence of systemic inflammation and, in different animals, induce systemic inflammation not inducing fever). Compare inflammation and fever for differential patterns of brain activation using immediate early gene cFOS expression in (amygdala, frontal cortex, hippocampus, hypothalamus, striatum, nucleus accumbens, locus ceruleus and others). Compare Inflammation and fever for their effects on brain metabolism (brain oxygen, glucose and lactate levels measured in vivo, in real-time). 2) Assess the impact of these different paradigms on behavioral measures (both positive and negative symptoms), relevant to autism spectrum disorders in 3 model systems with complementary advantages a.C58/J: Natural mutant showing both positive and negative symptoms relevant to ASD (#000669). b.B6.129-Shank3tm2Gfng/J (# 017688; also known as Shank3B-) c.Tsc+/-: B6;129S4-Tsc2tm1Djk/J (#004686) 3) We will pursue preliminary evidence for: Involvement of specific inflammatory pathways (PGE2, IL-1β; TNF) and of altered autophagy
  Funding Agency

  SIMONS FOUNDATION
  Date From

  April 2017
  Date To

  March 2019
• Title

  Neuroinflammatory and cognitive consequences of losing cholinergic anti-inflammatory tone in the forebrain
  Summary

  Systemic inflammation can trigger acute cognitive dysfunction (including delirium) as well as accelerating long-term cognitive decline (including dementia) and this occurs with high prevalence in the aging population. It is accepted that prior neurodegeneration increases the risk of these adverse health outcomes but this is poorly understood and we now propose that loss of anti-inflammatory acetylcholinergic tone predisposes to exaggerated brain inflammatory responses to systemic inflammatory insults, resulting in excessive inflammatory mediator release and contributing to acute cognitive dysfunction and lasting brain injury. In the current proposal we will use p75NTR-saporin to produce partial and selective degeneration of basal forebrain cholinergic neurons, and will induce systemic inflammation with bacterial endotoxin or polymicrobial sepsis, in order to study the influence of pre-existing hypocholinergia on acute illness-induced brain inflammation, changes in brain energy metabolism and neurophysiology (time-synchronized to behaviour) and new brain injury leading to long-term cognitive decline.
  Funding Agency

  National Institutes of Health (USA)
  Date From

  2016
  Date To

  2021

Neurosciences, Clinical and health psychology, Immunology, Other clinical medicine, Biochemistry and cell biology,

• Wellcome Trust Senior Research Fellowship 2010
• Wellcome Trust Research Career Development Fellowship 2006

• Psychoneuroimmunology Research Society 2014
• Society for Neuroscience 2015
• European Delirium Association 2017

• As a member of the Association Executive I have contributed to discussions leading to a consensus adopted by the European Delirium Association and the American Delirium Society (BMC Medicine 201412:141 DOI: 10.1186/s12916-014-0141-2) that with respect to "The DSM-5 criteria, level of arousal and delirium diagnosis: inclusiveness is safer". I was also part of an international panel of experts gathered to write a definitive report on the "Intensive Care Medicine Research Agenda on Delirium" for publication in INTENSIVE CARE MEDICINE. I am an editorial board member of 2 journals: Brain Behavior and Immunity. Journal of Neuroinflammation.