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Dr. Colm Cunningham
Associate Professor - Neuroscience, Biochemistry
Associate Professor - Neuroscience, Trinity Inst. of Neurosciences (TCIN)

Publications and Further Research Outputs

Peer-Reviewed Publications

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), 2024 Journal Article, 2024 DOI

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), 2024 Journal Article, 2024 DOI

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, p215-223 Journal Article, 2024 DOI

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, p81-108 Journal Article, 2024 DOI

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, p2150-2174 Journal 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, p2132-2141 Journal Article, 2023 DOI

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 - 3411 Journal Article, 2023 DOI

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), 2023 Journal Article, 2023 DOI

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, 2023 Journal Article, 2023 DOI

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), 2023 Journal Article, 2023 DOI

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, p219-238 Journal Article, 2022 TARA - Full Text DOI

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 BrÎne, 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, p3458-3483 Journal Article, 2022 DOI

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-e241 Journal Article, 2022 DOI

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, p413-428 Journal Article, 2021 TARA - Full Text DOI

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, p357-368 Journal Article, 2021 TARA - Full Text DOI

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, p312-325 Journal Article, 2021 TARA - Full Text DOI

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, p1735-1755 Journal Article, 2021 TARA - Full Text DOI

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.2876-19.2020 Journal Article, 2020 TARA - Full Text

Wilson, J.E., Mart, M.F., Cunningham, C. et al., Delirium, Nat Rev Dis Primers , 6, (90), 2020 Journal Article, 2020 DOI 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, p711-725 Journal Article, 2020 TARA - Full Text DOI

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, p726-733 Journal Article, 2020 DOI TARA - Full Text

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), 2020 Journal Article, 2020 TARA - Full Text DOI

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, p932-933 Journal Article, 2020 DOI TARA - Full Text

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), 2019 Journal Article, 2019 DOI

Eckenhoff, M.F. and Cunningham, C., Animal Models and Cognitive Testing of Perioperative Neurocognitive Disorders, 2019, 61-81pp Book, 2019 DOI

Cunningham, C. and Dunne, A. and Lopez-Rodriguez, A.B., Astrocytes: Heterogeneous and Dynamic Phenotypes in Neurodegeneration and Innate Immunity, Neuroscientist, 2019, p455-474 Journal Article, 2019 TARA - Full Text DOI

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, 2019 Journal Article, 2019 URL DOI

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, p1566 Journal Article, 2019 DOI

Neher J.J, Cunningham C, Priming Microglia for Innate Immune Memory in the Brain, Trends in Immunology, 40, (4), 2019, p358 - 374 Journal Article, 2019 URL DOI

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, p579-591 Journal Article, 2019 DOI

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 - 1276 Journal Article, 2019 TARA - Full Text DOI

Arora R.C, Cunningham C, Losing sleep over delirium, Critical Care Medicine, 46, (6), 2018, p1036 - 1038 Journal Article, 2018 DOI URL

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, p64-74 Journal Article, 2018 TARA - Full Text DOI

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 - 847 Journal Article, 2018 URL DOI

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, p93-101 Journal Article, 2018 DOI

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 TARA - Full Text DOI

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, p2029-2039 Journal 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, p244-251 Journal Article, 2017 DOI

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, p1329-1339 Journal Article, 2017 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 - 244 Journal Article, 2017 URL 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 - 608 Journal Article, 2016 DOI

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 - 797 Journal Article, 2015 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, p843-852 Journal Article, 2015 DOI

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, p812-825 Journal Article, 2015 TARA - Full Text DOI

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 - 8422 Journal Article, 2015 URL

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

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, 403-415 Journal Article, 2015 TARA - Full Text DOI

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, 274-286 Journal Article, 2015 TARA - Full Text

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

Sanders, R.D. Coburn, M. Cunningham, C. Pandharipande, P., Risk factors for postoperative delirium, The Lancet Psychiatry, 1, (6), 2014, p404 - 406 Journal Article, 2014 URL DOI

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 TARA - Full Text 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 - 225 Journal Article, 2014 URL TARA - Full Text DOI

Cunningham C, Microglia and neurodegeneration: The role of systemic inflammation, GLIA, 61, 2013, p71 - 90 Journal Article, 2013 URL

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

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, pe69123 Journal Article, 2013 DOI TARA - Full Text

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 TARA - Full Text DOI

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, p280-296 Journal Article, 2013

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, 719-731 Journal Article, 2013

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 - 13 Journal Article, 2013 URL 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, p667-74 Journal 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, p15248-58 Journal Article, 2013 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, pe78385 Journal Article, 2013 TARA - Full Text DOI

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, p60-73 Journal Article, 2012 TARA - Full Text DOI

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 - 1566 Journal Article, 2012 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.e3 Journal Article, 2012 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

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 - 6294 Journal Article, 2012 URL TARA - Full Text DOI

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, p2809-16 Journal Article, 2012 TARA - Full Text DOI

Colm Cunningham, Systemic inflammation and delirium: important co-factors in the progression of dementia, Biochemical Society Transactions, 39, 2011, p945 - 953 Review Article, 2011 DOI 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 - 218 Journal Article, 2011 URL DOI

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, p615-22 Journal Article, 2011 DOI

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), 2011 Journal Article, 2011 TARA - Full Text

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, 215-227 Journal Article, 2011

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, p1151-1153 Journal Article, 2011 DOI

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), 2011 Journal Article, 2011 TARA - Full Text

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 - 2030 Journal Article, 2010 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, p409-19 Journal Article, 2010 DOI

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, p996-1007 Journal Article, 2010

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 - 312 Journal Article, 2009 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 - 111 Journal 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 - 774 Journal 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 - 1814 Journal 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 - 1127 Journal 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 - 238 Journal 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 - 7 Journal 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 - 29 Journal Article, 2008 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, p2231-2244 Journal 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, p299-306 Journal Article, 2008 DOI

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, p836-850 Journal Article, 2007

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 - 502 Journal Article, 2007 DOI

Perry, V.H., Cunningham, C. and Holmes, C, Systemic infections affect chronic neurodegeneration, Nature Reviews Immunology, 7, (2), 2007, p161 - 167 Journal Article, 2007 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, p638-650 Journal Article, 2006 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, p5174-5184 Journal Article, 2005

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, p283-295 Journal Article, 2005 DOI

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, p258-269 Journal Article, 2005 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, p9275-9284 Journal Article, 2005 DOI

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

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, p292-303 Journal Article, 2004 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, p2147-2155 Journal Article, 2003 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, p1174-1182 Journal Article, 2003 DOI

Perry V.H., Newman, T.A. Cunningham, C, The impact of systemic infection on neurodegenerative disease, Nature reviews Neuroscience, 4, (February), 2003, p103 - 112 Journal 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

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, p107-119 Journal Article, 2002

Perry, V.H., Cunningham, C. and Boche, Atypical inflammation in the central nervous system in prion disease, Current Opinion in Neurology , 15, 2002, p349-354 Journal Article, 2002 DOI

Combrinck, M.I., Perry, V.H. and Cunningham C., Peripheral infection evokes exaggerated sickness behaviour in pre-clinical murine prion disease, Neuroscience., 112, 2002, p7-11 Journal Article, 2002 DOI

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, p866-871 Journal 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, p109-21 Journal 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

Delinquency in, Irish Families Under Stress Volume 3, Dublin, Ireland, E.H.B.: Dublin, 1991, pp166 - 184, [Fitzgerald M. ] Book Chapter, 1991

Non-Peer-Reviewed Publications

Colm Cunningham, European Delirium Association annual meeting 2017, Oslo, Autumn, 2017 Invited Talk, 2017

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, 2017 Dataset, 2017

Colm Cunningham, American Delirium Society Annual Meeting, Nashville, June, 2016 Invited Talk, 2016

Colm Cunningham, Neurosciences in Intensive Care Symposium, Pasteur institute, Paris, June, 2016 Invited Talk, 2016

Colm Cunningham, Immunology research series, University of Cambridge, October, 2016 Invited Talk, 2016

Colm Cunningham, British Association for Psychopharmacology Conference, Bristol, August, 2015, BAP Invited Talk, 2015

Colm Cunningham, Keynote lecture, European Delirium Associaton/British Geriatric Society Meeting, London, September, 2015, BGS/EDA Invited Talk, 2015

Colm Cunningham, "Delirium in Older Adults: Finding Order in the Disorder", , NIH, Bethesda, Maryland, USA, February, 2014, National Institute of Aging & American Geriatrics Society Invited Talk, 2014

Robert Dantzer(ed.), Cytokines in the ageing brain, Trends in Neurosciences, Arcachon, France, 25, ((11)), June 2002, Elsevier, 2002, 546-547 p Proceedings of a Conference, 2002 DOI

Research Expertise

Projects

  • 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
    • 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
  • 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
    • 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

Keywords

Ageing, Older People and Healthcare; Aging/Gerontology; Alzheimer's Disease; Amyotrophic Lateral Sclerosis (ALS); Animal Models; Brain; Dementia; Dementia/ Alzheimer's Disease; Depression; Emotional/Mental Health--Geriatric; Inflammation; Neurodegeneration; Neurodegenerative Diseases/Disorders; Neurological Disorders; Parkinson's Disease; Senile Dementia; Stress

Recognition

Representations

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.

Awards and Honours

Wellcome Trust Research Career Development Fellowship 2006

Wellcome Trust Senior Research Fellowship 2010

Memberships

European Delirium Association 2008 – 2017

Society for Neuroscience 2005 – 2015

Psychoneuroimmunology Research Society 2009 – 2014