Group name: Experimental Neuropathology
Group leader: Daniel C. Anthony
Group members: Dr Fay Probert, Dr Tianrong Yeo, Jay Roodselaar, Kim Wals, Amelie Gavard, Dr Megan Sealey, Yifan Zhou, Dr Marcia Kronka, Inês Sá-Pereira, Cristina Simogoloukarali, Isla Hazelton & Ashely Dale
Department & University/Hospital/Other: IMM - Department of Neurobiology Research and the Department of Pharmacology at the University of Oxford
Funding sources: MRC, Spinal Research, Merck GMSI, MS Society UK
Description of research:
I Have lead a team who have sought to discover how infection or injury contributes to the outcome of distinct brain pathologies. We have made a number of important discoveries in recent years that have generated collaborations and initiated research programmes in other independent laboratories among which I would highlight the following:
1. Different CNS compartments exhibit distinct responses to cytokines and the aged brain also responds differently to inflammatory challenges;
2. That the liver synthesises chemokines to mobilise immune cells to the blood for subsequent entry to diseased tissue - this pivotal feature of the innate inflammatory response was unknown prior to our studies;
3. That focal MS-like lesions can be reactivated by systemic infections;
4. That a 'window of susceptibility' to inflammatory stimuli exists in infant animals;
5. That TNF induces distinct vascular changes in the brain that lead to the recruitment og platelets and monocytes, which contributes to the outcome og cerebral malaria;
6. That endogenous extracellular vesicles (EVs) are responsible for a brain-liver communication and that changes in the circulating population of can result in alternations in animal behavior;
7. That NMR-based metabolimics can be used to identify distinct CNS pathologies;
8. And that post-translational modifications can be used to generate new targeting agents.
Indeed our imaging studies were the first to show that targeted MRI contrast agents could be used to detect disease in the brain that is not visible with any other imaging modality (MRM 2004, Nature Medicine 2007). This work led to the award of a MRC DPFS translational grant (2010-17) and the formation of a spin-out company.
Key publications (last 10 years):
(Year 2016-2017 of a total 141 articles).
Google Scholar: h=44, cit. 7267, Scopus h=39, cit. 5402
Articles and reviews (First, *corresponding author, OR SENIOR AUTHOR: n=62))
141. Hazleton I, Yates A, Dale A, Roodselaar J, Akbar N, Ruitenberg M, Anthony DC, Couch Y. Exacerbation of acute traumatic brain injury by circulating extracellular vesicles. J Neurotrauma. 2017 Nov 17. doi: 10.1089/neu.2017.5049140
140. Mardiguian S, Ladds E, Turner R, Shepherd H, Campbell SJ, Anthony DC. The Contribution of the Acute Phase Response to the pathogenesis of relapse in Chronic-Relapsing Experimental Autoimmune Encephalitis models of Multiple Sclerosis. J Neuroinflammation (2017) Sep 30;14(1):196. doi: 10.1186/s12974-017-0969-4.
139. Akbar N, Digby JE, Cahill TJ, Tavare AN, Corbin AL, Saluja S, Dawkins S, Edgar L, Rawlings N, Ziberna K, McNeill E; Oxford Acute Myocardial Infarction (OxAMI) Study, Johnson E, Aljabali AA, Dragovic RA, Rohling M, Belgard TG, Udalova IA, Greaves DR, Channon KM, Riley PR, Anthony DC, Choudhury RP. Endothelium-derived extracellular vesicles promote splenic monocyte mobilisation in myocardial infarction. JCI Insight. (2017) Sep 7;2(17). pii: 93344. doi: 10.1172/jci.insight.93344.
138. Couch Y, Akbar N, Roodselaar J, Evans MC, Gardiner C, Sargent I, Romero I, Bristow A, Buchan A, Haughey N, and Anthony D. Circulating endothelial cell-derived extracellular vesicles mediate the acute phase response and sickness behaviour associated with CNS inflammation. Scientific Reports. Sci Rep. (2017) Aug 29;7(1):9574. doi: 10.1038/s41598-017-09710-3.
137. Vignisse J, Sambon M, Gorlova A, Pavlov D, Caron N, Malgrange B, Shevtsova E, Svistunov A, Anthony DC, Markova N, Bazhenova N, Coumans B, Lakaye B, Wins P, Strekalova T, Lucien Bettendorff L.Thiamine and benfotiamine prevent stress-induced suppression of hippocampal neurogenesis in mice exposed to predation without affecting brain thiamine diphosphate levels. Mol Cell Neurosci. (2017) Jul;82:126-136. doi: 10.1016/j.mcn.2017.05.005.
136. Dickens AM, Tovar-Y-Romo LB, Yoo SW, Trout AL, Bae M, Kanmogne M, Megra B, Williams DW, Witwer KW, Gacias M, Tabatadze N, Cole RN, Casaccia P, Berman JW, Anthony DC, Haughey NJ. Astrocyte-shed extracellular vesicles regulate the peripheral leukocyte response to inflammatory brain lesions. Sci Signal. (2017) Apr 4;10(473).
135. Veniaminova E, Cespuglio R, Cheung CW, Umriukhin A, Markova N, Shevtsova E, Lesch KP, Anthony DC and Strekalova T. Autism-like behaviours and memory deficits result from a Western diet in mice. Neural Plast. (2017) 9498247. doi: 10.1155/2017/9498247.
134. Perez-Balderas F, van Kasteren SI, Aljabali A, Serres S, Jefferson A, Sarmiento-Soto M, Khrapitchev AA, Larkin JR, Bristow C, Lee SS, Bort G, De Simone F, Campbell SJ, Choudhury RP, (Anthony DC*, Sibson NR*, Davis BG*). Covalent assembly of nanoparticles as a peptidase-degradable platform for molecular MRI. Nat Commun. (2017) 8:14254. doi: 10.1038/ncomms14254.
133. Gredal H, Thomsen BB, Boza-Serrano A, Garosi L, Rusbridge C, Anthony D, Møller A, Finsen B, Deierborg T, Lambertsen KL, Berendt M. Interleukin-6 is increased in plasma and cerebrospinal fluid of community-dwelling domestic dogs with acute ischaemic stroke. Neuroreport. (2017) doi: 10.1097/WNR.0000000000000728
132. Bento-Torres J, Sobral LL, Reis R, de Oliveira R, Anthony D.C, Vasconcelos P.F.C, and Diniz C. Age and environment influences on mouse prion disease progression: behavioral changes and morphometry and stereology of hippocampal astrocytes. Oxid Med Cell Longev. (2017):4504925.
Other outputs e.g. patents, novel therapies etc:
6 patents granted
Key collaborations:
Danish:
Kate Lykke Lambertsen, Bente Finsen, and Trevor Owens
IMM - Department of Neurobiology Research
International:
Norman Haughey, Hopkins, USA
Robin Choudhury, Oxford, UK
Ben Davis, Oxford, UK
Ignacio A. Romero, Open University, UK
Dave Carter, Oxford Brookes, UK
Cristovam W Picanço Diniz, Belem, Brazil
Rubem Guedes, Recife, Brazil
Tatyana Strekalova, Moscow, Russia
Dorian McGavern, ninds, nih, USA
Alex Dickens, Turku, Finland
David Leppert, Basel, Switzerland
Zsolt Bagi, Augusta, USA
Marc Ruitenberg, University of Queensland, Australia
Marc Combrinck, University of Cape Town, South Africa
Infrastructure:
Beyond standard laboratory tecniques, we are equipped for NMR metabolomics, in vivo rat and mouse models of neuroinflammation, and autoradiolography for F-18 and H-3.