Professor Richard Reynolds, BSc AKC PhD

Choi SR, Howell OW, Carassiti D, Magliozzi R, Gveric D, Muraro PA, Nicholas R, Roncaroli F, Reynolds Ret al., 2012, Meningeal inflammation plays a role in the pathology of primary progressive multiple sclerosis, BRAIN, Vol: 135, Pages: 2925-2937, ISSN: 0006-8950

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• Citations: 253

Campbell GR, Kraytsberg Y, Krishnan KJ, Ohno N, Ziabreva I, Reeve A, Trapp BD, Newcombe J, Reynolds R, Lassmann H, Khrapko K, Turnbull DM, Mahad DJet al., 2012, Clonally expanded mitochondrial DNA deletions within the choroid plexus in multiple sclerosis, ACTA NEUROPATHOLOGICA, Vol: 124, Pages: 209-220, ISSN: 0001-6322

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• Citations: 27

Politis M, Giannetti P, Su P, Turkheimer F, Keihaninejad S, Wu K, Waldman A, Malik O, Matthews PM, Reynolds R, Nicholas R, Piccini Pet al., 2012, Increased PK11195 PET binding in the cortex of patients with MS correlates with disability, NEUROLOGY, Vol: 79, Pages: 523-530, ISSN: 0028-3878

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• Citations: 131

Markoullis K, Sargiannidou I, Gardner C, Hadjisavvas A, Reynolds R, Kleopa KAet al., 2012, Disruption of oligodendrocyte gap junctions in experimental autoimmune encephalomyelitis, GLIA, Vol: 60, Pages: 1053-1066, ISSN: 0894-1491

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• Citations: 59

Markoullis K, Sargiannidou I, Schiza N, Hadjisavvas A, Roncaroli F, Reynolds R, Kleopa KAet al., 2012, Gap junction pathology in multiple sclerosis lesions and normal-appearing white matter, ACTA NEUROPATHOLOGICA, Vol: 123, Pages: 873-886, ISSN: 0001-6322

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• Citations: 62

Durrenberger PF, Ettorre A, Kamel F, Webb LV, Sim M, Nicholas RS, Malik O, Reynolds R, Boyton RJ, Altmann DMet al., 2012, Innate Immunity in multiple sclerosis white matter lesions: expression of natural cytotoxicity triggering receptor 1 (NCR1), Journal of Neuroinflammation, Vol: 9, ISSN: 1742-2094

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Durrenberger PF, Gruenblatt E, Fernando FS, Monoranu CM, Evans J, Riederer P, Reynolds R, Dexter DTet al., 2012, Inflammatory Pathways in Parkinson's Disease; A BNE Microarray Study, PARKINSONS DISEASE, Vol: 2012, ISSN: 2090-8083

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• Citations: 44

Swingland JT, Durrenberger PF, Reynolds R, Dexter DT, Pombo A, Deprez M, Roncaroli F, Turkheimer FEet al., 2012, Mean expression of the X-chromosome is associated with neuronal density, FRONTIERS IN NEUROSCIENCE, Vol: 6, ISSN: 1662-453X

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• Citations: 9

Schirmer L, Rothhammer V, Petermann F, Carassiti D, Grummel V, Reynolds R, Hemmer B, Korn Tet al., 2011, Enrichment of CD161+CCR6+gamma delta T cells in the CSF of multiple sclerosis patients, MULTIPLE SCLEROSIS JOURNAL, Vol: 17, Pages: S29-S30, ISSN: 1352-4585

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Howell OW, Reeves CA, Nicholas R, Carassiti D, Radotra B, Gentleman SM, Serafini B, Aloisi F, Roncaroli F, Magliozzi R, Reynolds Ret al., 2011, Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis, BRAIN, Vol: 134, Pages: 2755-2771, ISSN: 0006-8950

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• Citations: 555

Sawcer S, Hellenthal G, Pirinen M, Spencer CCA, Patsopoulos NA, Moutsianas L, Dilthey A, Su Z, Freeman C, Hunt SE, Edkins S, Gray E, Booth DR, Potter SC, Goris A, Band G, Oturai AB, Strange A, Saarela J, Bellenguez C, Fontaine B, Gillman M, Hemmer B, Gwilliam R, Zipp F, Jayakumar A, Martin R, Leslie S, Hawkins S, Giannoulatou E, D'alfonso S, Blackburn H, Boneschi FM, Liddle J, Harbo HF, Perez ML, Spurkland A, Waller MJ, Mycko MP, Ricketts M, Comabella M, Hammond N, Kockum I, McCann OT, Ban M, Whittaker P, Kemppinen A, Weston P, Hawkins C, Widaa S, Zajicek J, Dronov S, Robertson N, Bumpstead SJ, Barcellos LF, Ravindrarajah R, Abraham R, Alfredsson L, Ardlie K, Aubin C, Baker A, Baker K, Baranzini SE, Bergamaschi L, Bergamaschi R, Bernstein A, Berthele A, Boggild M, Bradfield JP, Brassat D, Broadley SA, Buck D, Butzkueven H, Capra R, Carroll WM, Cavalla P, Celius EG, Cepok S, Chiavacci R, Clerget-Darpoux F, Clysters K, Comi G, Cossburn M, Cournu-Rebeix I, Cox MB, Cozen W, Cree BAC, Cross AH, Cusi D, Daly MJ, Davis E, de Bakker PIW, Debouverie M, D'hooghe MB, Dixon K, Dobosi R, Dubois B, Ellinghaus D, Elovaara I, Esposito F, Fontenille C, Foote S, Franke A, Galimberti D, Ghezzi A, Glessner J, Gomez R, Gout O, Graham C, Grant SFA, Guerini FR, Hakonarson H, Hall P, Hamsten A, Hartung H-P, Heard RN, Heath S, Hobart J, Hoshi M, Infante-Duarte C, Ingram G, Ingram W, Islam T, Jagodic M, Kabesch M, Kermode AG, Kilpatrick TJ, Kim C, Klopp N, Koivisto K, Larsson M, Lathrop M, Lechner-Scott JS, Leone MA, Leppa V, Liljedahl U, Bomfim IL, Lincoln RR, Link J, Liu J, Lorentzen AR, Lupoli S, Macciardi F, Mack T, Marriott M, Martinelli V, Mason D, McCauley JL, Mentch F, Mero I-L, Mihalova T, Montalban X, Mottershead J, Myhr K-M, Naldi P, Ollier W, Page A, Palotie A, Pelletier J, Piccio L, Pickersgill T, Piehl F, Pobywajlo S, Quach HL, Ramsay PP, Reunanen M, Reynolds R, Rioux J, Rodegher M, Roesner S, Rubio JP, Rueckert I-M, Salvetti M, Salvi E, Santaniello A, Schaefer CA, Schreiber Set al., 2011, Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis, NATURE, Vol: 476, Pages: 214-219, ISSN: 0028-0836

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• Citations: 1975

Reynolds R, Roncaroli F, Nicholas R, Radotra B, Gveric D, Howell Oet al., 2011, The neuropathological basis of clinical progression in multiple sclerosis, ACTA NEUROPATHOLOGICA, Vol: 122, Pages: 155-170, ISSN: 0001-6322

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• Citations: 150

Schmitt A, Leonardi-Essmann F, Durrenberger PF, Parlapani E, Schneider-Axmann T, Spanagel R, Arzberger T, Kretzschmar H, Herrera-Marschitz M, Gruber O, Reynolds R, Falkai P, Gebicke-Haerter PJet al., 2011, Regulation of immune-modulatory genes in left superior temporal cortex of schizophrenia patients: a genome-wide microarray study, WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY, Vol: 12, Pages: 201-215, ISSN: 1562-2975

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• Citations: 59

Sun G, Reynolds R, Leclerc I, Rutter GAet al., 2011, <i>RIP2</i>-mediated <i>LKB1</i> deletion causes axon degeneration in the spinal cord and hind-limb paralysis, DISEASE MODELS & MECHANISMS, Vol: 4, Pages: 193-U72, ISSN: 1754-8403

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• Citations: 23

Campbell GR, Ziabreva I, Reeve AK, Krishnan KJ, Reynolds R, Howell O, Lassmann H, Turnbull DM, Mahad DJet al., 2011, Mitochondrial DNA Deletions and Neurodegeneration in Multiple Sclerosis, ANNALS OF NEUROLOGY, Vol: 69, Pages: 481-492, ISSN: 0364-5134

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• Citations: 255

Owen DRJ, Lewis AJM, Reynolds R, Rupprecht R, Eser D, Wilkins MR, Bennacef I, Nutt DJ, Parker CAet al., 2011, Variation in Binding Affinity of the Novel Anxiolytic XBD173 for the 18 kDa Translocator Protein in Human Brain, SYNAPSE, Vol: 65, Pages: 257-259, ISSN: 0887-4476

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• Citations: 43

Lovato L, Willis SN, Rodig SJ, Caron T, Almendinger SE, Howell OW, Reynolds R, O'Connor KC, Hafler DAet al., 2011, Related B cell clones populate the meninges and parenchyma of patients with multiple sclerosis, BRAIN, Vol: 134, Pages: 534-541, ISSN: 0006-8950

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• Citations: 151

Owen DR, Gunn RN, Rabiner EA, Bennacef I, Fujita M, Kreisl WC, Innis RB, Pike VW, Reynolds R, Matthews PM, Parker CAet al., 2011, Mixed-affinity binding in humans with 18-kDa translocator protein ligands, J Nucl Med, Vol: 52, Pages: 24-32, ISSN: 1535-5667

11C-PBR28 PET can detect the 18-kDa translocator protein (TSPO) expressed within macrophages. However, quantitative evaluation of the signal in brain tissue from donors with multiple sclerosis (MS) shows that PBR28 binds the TSPO with high affinity (binding affinity [Ki], approximately 4 nM), low affinity (Ki, approximately 200 nM), or mixed affinity (2 sites with Ki, approximately 4 nM and approximately 300 nM). Our study tested whether similar binding behavior could be detected in brain tissue from donors with no history of neurologic disease, with TSPO-binding PET ligands other than 11C-PBR28, for TSPO present in peripheral blood, and with human brain PET data acquired in vivo with 11C-PBR28. METHODS: The affinity of TSPO ligands was measured in the human brain postmortem from donors with a history of MS (n=13), donors without any history of neurologic disease (n=20), and in platelets from healthy volunteers (n=13). Binding potential estimates from thirty-five 11C-PBR28 PET scans from an independent sample of healthy volunteers were analyzed using a gaussian mixture model. RESULTS: Three binding affinity patterns were found in brains from subjects without neurologic disease in similar proportions to those reported previously from studies of MS brains. TSPO ligands showed substantial differences in affinity between subjects classified as high-affinity binders (HABs) and low-affinity binders (LABs). Differences in affinity between HABs and LABs are approximately 50-fold with PBR28, approximately 17-fold with PBR06, and approximately 4-fold with DAA1106, DPA713, and PBR111. Where differences in affinity between HABs and LABs were low ( approximately 4-fold), distinct affinities were not resolvable in binding curves for mixed-affinity binders (MABs), which appeared to express 1 class of sites with an affinity approximately equal to the mean of those for HABs and LABs. Mixed-affinity binding was detected in platelets from an independent sample (HAB, 69%; MAB, 31%), al

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Aloisi F, Serafini B, Magliozzi R, Howell OW, Reynolds Ret al., 2010, Detection of Epstein-Barr virus and B-cell follicles in the multiple sclerosis brain: what you find depends on how and where you look, BRAIN, Vol: 133, ISSN: 0006-8950

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• Citations: 62

Magliozzi R, Howell OW, Reeves C, Roncaroli F, Nicholas R, Serafini B, Aloisi F, Reynolds Ret al., 2010, A Gradient of Neuronal Loss and Meningeal Inflammation in Multiple Sclerosis, ANNALS OF NEUROLOGY, Vol: 68, Pages: 477-493, ISSN: 0364-5134

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• Citations: 493

Howell OW, Rundle JL, Garg A, Komada M, Brophy PJ, Reynolds Ret al., 2010, Activated Microglia Mediate Axoglial Disruption That Contributes to Axonal Injury in Multiple Sclerosis, JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, Vol: 69, Pages: 1017-1033, ISSN: 0022-3069

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• Citations: 171

Androdias G, Reynolds R, Chanal M, Ritleng C, Confavreux C, Nataf Set al., 2010, Meningeal T Cells Associate with Diffuse Axonal Loss in Multiple Sclerosis Spinal Cords, ANNALS OF NEUROLOGY, Vol: 68, Pages: 465-476, ISSN: 0364-5134

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• Citations: 92

Serafini B, Severa M, Columba-Cabezas S, Rosicarelli B, Veroni C, Chiappetta G, Magliozzi R, Reynolds R, Coccia EM, Aloisi Fet al., 2010, Epstein-Barr Virus Latent Infection and BAFF Expression in B Cells in the Multiple Sclerosis Brain: Implications for Viral Persistence and Intrathecal B-Cell Activation, JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, Vol: 69, Pages: 677-693, ISSN: 0022-3069

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• Citations: 122

Amadio S, Montilli C, Magliozzi R, Bernardi G, Reynolds R, Volonte Cet al., 2010, P2Y₁₂ Receptor Protein in Cortical Gray Matter Lesions in Multiple Sclerosis, CEREBRAL CORTEX, Vol: 20, Pages: 1263-1273, ISSN: 1047-3211

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• Citations: 57

Anderson JM, Patani R, Reynolds R, Nicholas R, Compston A, Spillantini MG, Chandran Set al., 2010, Abnormal tau phosphorylation in primary progressive multiple sclerosis, ACTA NEUROPATHOLOGICA, Vol: 119, Pages: 591-600, ISSN: 0001-6322

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• Citations: 26

Papadopoulos D, Rundle J, Patel R, Marshall I, Stretton J, Eaton R, Richardson JC, Gonzalez MI, Philpott KL, Reynolds Ret al., 2010, FTY720 Ameliorates MOG-Induced Experimental Autoimmune Encephalomyelitis by Suppressing Both Cellular and Humoral Immune Responses, JOURNAL OF NEUROSCIENCE RESEARCH, Vol: 88, Pages: 346-359, ISSN: 0360-4012

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• Citations: 51

Kim JY, Shen S, Dietz K, He Y, Howell O, Reynolds R, Casaccia Pet al., 2010, HDAC1 nuclear export induced by pathological conditions is essential for the onset of axonal damage, NATURE NEUROSCIENCE, Vol: 13, Pages: 180-U63, ISSN: 1097-6256

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• Citations: 163

Durrenberger PF, Fernando S, Kashefi SN, Ferrer I, Hauw J-J, Seilhean D, Smith C, Walker R, Al-Sarraj S, Troakes C, Palkovits M, Kasztner M, Huitinga I, Arzberger T, Dexter DT, Kretzschmar H, Reynolds Ret al., 2010, Effects of Antemortem and Postmortem Variables on Human Brain mRNA Quality: A BrainNet Europe Study, JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, Vol: 69, Pages: 70-81, ISSN: 0022-3069

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• Citations: 130

Owen DR, Howell OW, Tang SP, Wells LA, Bennacef I, Bergstrom M, Gunn RN, Rabiner EA, Wilkins MR, Reynolds R, Matthews PM, Parker CAet al., 2010, Two binding sites for [3H]PBR28 in human brain: implications for TSPO PET imaging of neuroinflammation, J Cereb Blood Flow Metab, Vol: 30, Pages: 1608-1618, ISSN: 1559-7016

[(11)C]PBR28, a radioligand targeting the translocator protein (TSPO), does not produce a specific binding signal in approximately 14% of healthy volunteers. This phenomenon has not been reported for [(11)C]PK11195, another TSPO radioligand. We measured the specific binding signals with [(3)H]PK11195 and [(3)H]PBR28 in brain tissue from 22 donors. Overall, 23% of the samples did not generate a visually detectable specific autoradiographic signal with [(3)H]PBR28, although all samples showed [(3)H]PK11195 binding. There was a marked reduction in the affinity of [(3)H]PBR28 for TSPO in samples with no visible [(3)H]PBR28 autoradiographic signal (K(i)=188+/-15.6 nmol/L), relative to those showing normal signal (K(i)=3.4+/-0.5 nmol/L, P<0.001). Of this latter group, [(3)H]PBR28 bound with a two-site fit in 40% of cases, with affinities (K(i)) of 4.0+/-2.4 nmol/L (high-affinity site) and 313+/-77 nmol/L (low-affinity site). There was no difference in K(d) or B(max) for [(3)H]PK11195 in samples showing no [(3)H]PBR28 autoradiographic signal relative to those showing normal [(3)H]PBR28 autoradiographic signal. [(3)H]PK11195 bound with a single site for all samples. The existence of three different binding patterns with PBR28 (high-affinity binding (46%), low-affinity binding (23%), and two-site binding (31%)) suggests that a reduction in [(11)C]PBR28 binding may not be interpreted simply as a reduction in TSPO density. The functional significance of differences in binding characteristics warrants further investigation.

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Palser AL, Norman AL, Saffell JL, Reynolds Ret al., 2009, Neural Cell Adhesion Molecule Stimulates Survival of Premyelinating Oligodendrocytes Via the Fibroblast Growth Factor Receptor, JOURNAL OF NEUROSCIENCE RESEARCH, Vol: 87, Pages: 3356-3368, ISSN: 0360-4012

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• Citations: 15