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Integrated omics reveals disease-associated radial glia-like cells with epigenetically dysregulated interferon response in multiple sclerosis

Publication: Neuron

10 October 2025

Bongsoo Park, Alexandra M. Nicaise, Dimitrios Tsitsipatis, Liviu Pirvan, Daniel Zucha, Andi Munteanu, Pranathi Prasad, Miguel Larraz Lopez De Novales, Cristian Bulgaru, Rafael Kollyfas, Julia Whitten, Cory M.Willis, Luka Culig, Joseph Llewellyn, Rosana-Bristena Ionescu, Magdy Mekdad, Madalena B. C. Simões-Abade, Grzegorz Krzak, Jinshui Fan, Supriyo De, Matthew O.Ellis, Marta Suarez Cubero, Angeliki Spathopoulou, Luca Peruzzotti-Jametti, Tommaso Leonardi, Gabriel Balmus, Frank Edenhofer, Myriam Gorospe, Lukas Valihrach, Irina Mohorianu, Stefano Pluchino, Isabel Beerman
Summary 
Progressive multiple sclerosis (PMS) involves a persistent, maladaptive inflammatory process with numerous cellular drivers. We generated induced neural stem cells (iNSCs) from patient fibroblasts through a direct reprogramming protocol that preserved their epigenome,which revealed a PMS-specific hypome-thylation of lipid metabolism and interferon(IFN) signaling genes.S ingle-cell multi-omics uncovered a novel, disease-associated radial glia-like cell (DARG) subpopulation in PMS cell lines exhibiting senes-cence and potent IFN responsiveness driven by specific transcription factors. Functionally, PMS iNSCs induced paracrine senescence and inflammation onto control cells, which was inhibited upon senolytic treatment. We identified inPMS brains a distinct population of senescent, IFN-responsive DARGs that developmentally aligned with the trajectories of iNSCs in vitro and spatially associated with inflammatory glia in chronically active lesions. DARGs may sustain smoldering inflammation, unveiling a previously unrecognized cellular axis that could un-derpin mechanisms in neurodegeneration.  This discovery offers novel insights into disease mechanisms and highlights potential therapeutic targets.

Quantitative susceptibility mapping at 7 T in COVID-19: brainstem effects and outcome associations 

Publication: Brain

Catarina Rua, Betty Raman, Christopher T Rodgers, Virginia F J Newcombe, Anne Manktelow, Doris A Chatfield, Stephen J Sawcer, Joanne G Outtrim, Victoria C Lupson, Emmanuel A Stamatakis, Guy B Williams, William T Clarke, Lin Qiu, Martyn Ezra, Rory McDonald, Stuart Clare, Mark Cassar, Stefan Neubauer, Karen D Ersche, Edward T Bullmore, David K Menon, Kyle Pattinson, James B Rowe 

08 October 2024

Summary

Damage to the brainstem – the brain’s ‘control centre’ – is behind long-lasting physical and psychiatric effects of severe Covid-19 infection, a study suggests.

Using ultra-high-resolution scanners that can see the living brain in fine detail, researchers from the Universities of Cambridge and Oxford and supported by NIHR Cambridge and Oxford BRCs, were able to observe the damaging effects Covid-19 can have on the brain. Read the full news story.

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Decompressive Craniectomy versus Craniotomy for Acute Subdural Hematoma

Publication: New England Journal of Medicine

Peter J. Hutchinson, Hadie Adams, Midhun Mohan, Bhagavatula I. Devi,  Christopher Uff, Shumaila Hasan, Harry Mee, Mark H. Wilson, Deepak K. Gupta, M.Ch, Diederik Bulters, Ardalan Zolnourian, Catherine J. McMahon, Matthew G. Stovell, Yahia Z. Al-Tamimi, Manoj K. Tewari, Manjul Tripathi, Simon Thomson, Edoardo Viaroli, Antonio Belli, Andrew T. King, Adel E. Helmy, Ivan S. Timofeev, Sarah Pyne,Dhaval P. Shukla, Dhananjaya I. Bhat, Andrew R. Maas, Franco Servadei, Geoffrey T. Manley,Garry Barton, Carole Turner, David K. Menon, Barbara Gregson, and Angelos G. Kolias,

23 April 2023

Summary

A new trial has found – where possible – surgeons should replace the removed section of the skull following surgery to treat a form of brain bleed. Researchers say the approach will save patients undergoing skull reconstruction further down the line. Read the full story.

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Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses

Publication: Brain

Edward J. Needham,, Alexander L. Ren, Richard J. Digby, Emma J. Norton,  Soraya Ebrahimi, Joanne G. Outtrim, Doris A. Chatfield, Anne E. Manktelow,  Maya M. Leibowitz, Virginia F. J. Newcombe, Rainer Doffinger, Gabriela Barcenas-Morales,  Claudia Fonseca, Michael J. Taussig, Rowan M. Burnstein, Romit J. Samanta,  Cordelia Dunai, Nyarie Sithole, Nicholas J. Ashton, Henrik Zetterberg, Magnus Gisslén, Arden Edén,, Emelie Marklund, Peter J. M. Openshaw, Jake Dunning,  Michael J. Griffiths, Jonathan Cavanagh, Gerome Breen, Sarosh R. Irani,,  Anne Elmer, Nathalie Kingston,, Charlotte Summers,, John R. Bradley,,  Leonie S. Taams, Benedict D. Michael, Edward T. Bullmore, Kenneth G. C. Smith, Paul A. Lyons, Alasdair J. Coles, David K. Menon  and the Cambridge NeuroCOVID Group, the CITIID-NIHR COVID- BioResource Collaboration and Cambridge NIHR Clinical Research Facility

6 September 2022

Summary

COVID-19 is associated with neurological complications including stroke, delirium and encephalitis. Furthermore, a post-viral syndrome dominated by neuropsychiatric symptoms is common, and is seemingly unrelated to COVID-19 severity. The true frequency and underlying mechanisms of neurological injury are unknown, but exaggerated host inflammatory responses appear to be a key driver of COVID-19 severity.

Researchers investigated the dynamics of, and relationship between, serum markers of brain injury (neurofilament light [NfL], glial fibrillary acidic protein [GFAP] and total tau) and markers of dysregulated host response (autoantibody production and cytokine profiles) in 175 patients admitted with COVID-19 and 45 patients with influenza.

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Socio-economic disadvantage is associated with alterations in brain wiring economy

Publication: bioRxiv

Roma Siugzdaite,  Danyal Akarca, Amy Johnson,  Sofia Carozza,  Alexander L Anwyl-Irvine,  Stepheni Uh,  Tess Smith, Giacomo Bignardi,  Edwin Dalmaijer,  Duncan E. Astle

10 June 2022

Summary

The quality of a child’s social and physical environment is a key influence on brain development, educational attainment and mental wellbeing. However, there still remains a mechanistic gap in our understanding of how environmental influences converge on changes in the brain’s developmental trajectory. In a sample of 145 children with structural diffusion tensor imaging data, researchers used generative network modelling to simulate the emergence of whole brain network organisation.

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Multivariate profile and acute-phase correlates of cognitive deficits in a COVID-19 hospitalised cohort

Publication: eClinicalMedicine

Adam Hampshire, Doris A. Chatfield, Anne Manktelow, Amy Jolly, William Trender, Peter J. Hellyer, Martina Del Giovane, Virginia F.J. Newcombe, Joanne G. Outtrim, Ben Warne, Junaid Bhatti, Linda Pointon, Anne Elmer, Nyarie Sithole, John Bradley, Nathalie Kingston, Stephen J.Sawcer, Edward T. Bullmore, David K.Menon

3 May 2022

Summary

Cognitive impairment as a result of severe COVID-19 is similar to that sustained between 50 and 70 years of age and is the equivalent to losing 10 IQ points. The results of the study suggest the effects are still detectable more than six months after the acute illness, and that any recovery is at best gradual. Read the full story 

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Brain charts for the human lifespan

Publication: Nature

R. A. I. Bethlehem, J. Seidlitz, S. R. White, J. W. Vogel, K. M. Anderson, C. Adamson, S. Adler, G. S. Alexopoulos, E. Anagnostou, A. Areces-Gonzalez, D. E. Astle, B. Auyeung,
M. Ayub, J. Bae, G. Ball, S. Baron-Cohen, R. Beare, S. A. Bedford, V. Benegal, F. Beyer, J. Blangero, M. Blesa Cábez, J. P. Boardman, M. Borzage, J. F. Bosch-Bayard, N. Bourke, V. D. Calhoun, M. M. Chakravarty, C. Chen, C. Chertavian, G. Chetelat, Y. S. Chong, J. H. Cole, A. Corvin, M. Costantino, E. Courchesne, F. Crivello, V. L. Cropley, J. Crosbie, N. Crossley, M. Delarue, R. Delorme, S. Desrivieres, G. A. Devenyi, M. A. Di Biase, R. Dolan, K. A. Donald, G. Donohoe, K. Dunlop, A. D. Edwards, J. T. Elison, C. T. Ellis, J. A. Elman, L. Eyler, D. A. Fair, E. Feczko, P. C. Fletcher, P. Fonagy, C. E. Franz, L. Galan-Garcia, A. Gholipour, J. Giedd, J. H. Gilmore, D. C. Glahn, I. M. Goodyer, P. E. Grant, N. A. Groenewold, F. M. Gunning, R. E. Gur, R. C. Gur, C. F. Hammill, O. Hansson, T. Hedden, A. Heinz, R. N. Henson, K. Heuer, J. Hoare, B. Holla, A. J. Holmes, R. Holt, H. Huang, K. Im, J. Ipser, C. R. Jack Jr, A. P. Jackowski, T. Jia, K. A. Johnson, P. B. Jones, D. T. Jones, R. S. Kahn, H. Karlsson, L. Karlsson, R. Kawashima, E. A. Kelley, S. Kern, K. W. Kim, M. G. Kitzbichler, W. S. Kremen, F. Lalonde, B. Landeau, S. Lee, J. Lerch, J. D. Lewis, J. Li, W. Liao, C. Liston, M. V. Lombardo, J. Lv, C. Lynch, T. T. Mallard, M. Marcelis, R. D. Markello, S. R. Mathias, B. Mazoyer, P. McGuire, M. J. Meaney, A. Mechelli, N. Medic, B. Misic, S. E. Morgan, D. Mothersill, J. Nigg, M. Q. W. Ong, C. Ortinau, R. Ossenkoppele, M. Ouyang, L. Palaniyappan, L. Paly, P. M. Pan, C. Pantelis, M. M. Park, T. Paus, Z. Pausova, D. Paz-Linares, A. Pichet Binette, K. Pierce, X. Qian, J. Qiu, A. Qiu, A. Raznahan, T. Rittman, A. Rodrigue, C. K. Rollins, R. Romero-Garcia, L. Ronan, M. D. Rosenberg, D. H. Rowitch, G. A. Salum, T. D. Satterthwaite, H. L. Schaare, R. J. Schachar, A. P. Schultz, G. Schumann, M. Schöll, D. Sharp, R. T. Shinohara, I. Skoog, C. D. Smyser, R. A. Sperling, D. J. Stein, A. Stolicyn, J. Suckling, G. Sullivan, Y. Taki, B. Thyreau, R. Toro, N. Traut, K. A. Tsvetanov, N. B. Turk-Browne, J. J. Tuulari, C. Tzourio, É. Vachon-Presseau, M. J. Valdes-Sosa, P. A. Valdes-Sosa, S. L. Valk, T. van Amelsvoort, S. N. Vandekar, L. Vasung, L. W. Victoria, S. Villeneuve, A. Villringer, P. E. Vértes, K. Wagstyl, Y. S. Wang, S. K. Warfield, V. Warrier, E. Westman, M. L. Westwater, H. C. Whalley, A. V. Witte, N. Yang, B. Yeo, H. Yun, A. Zalesky, H. J. Zar, A. Zettergren, J. H. Zhou, H. Ziauddeen, A. Zugman, X. N. Zuo, E. T. Bullmore & A. F. Alexander-Bloch

6 April 2022

Summary

An international team of researchers has created a series of brain charts spanning our entire lifespan – from a 15 week old fetus to 100 year old adult – that show how our brains expand rapidly in early life and slowly shrink as we age. Read the full story.

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Hospitalisation for COVID-19 predicts long lasting cerebrovascular impairment: A prospective observational cohort study

Publication: MedRxiv

Kamen A Tsvetanov, Lennart R B Spindler, Emmanuel A Stamatakis, Virginia FJ Newcombe, Victoria C Lupson, Doris A Chatfield, Anne E Manktelow, Joanne G Outtrim, Anne Elmer, Nathalie Kingston, John R Bradley, Edward T Bullmore, James B Rowe, David K Menon

02 February 2022

Summary

COVID-19 have seen multi-system effects that include neurological, vascular and neurovascular injury. Acute neurological sequelae are common, ranging from mild dizziness, headaches and anosmia to severe encephalitis, stroke and delirium. Researchers assessed the impact of COVID-19 on chronic cerebrovascular reactivity after hospitalisation.

Patients were recruited through the NIHR COVID-19 BioResource. Eligibility was based on admission to Addenbrookes Hospital with COVID-19 between 10th March 2020 and 31st July 2020, aged 18 years or older, survived the acute illness, and attended for a follow up visit, and no contradictions to MRI.

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Targeting Autoregulation-Guided Cerebral Perfusion Pressure after Traumatic Brain Injury (COGiTATE): A Feasibility Randomized Controlled Clinical Trial

Publication: Journal of Neurotrauma

Jeanette Tas, Erta Beqiri, Ruud C. van Kaam, Marek Czosnyka, Joseph Donnelly, Roel H. Haeren, Iwan C.C. van der Horst, Peter J. Hutchinson, Sander M.J. van Kuijk, Analisa L. Liberti, David K. Menon, Cornelia W.E. Hoedemaekers, Bart Depreitere, Peter Smielewski, Geert Meyfroidt, Ari Ercole, and Marcel J.H. Aries

12 October 2021

Summary

Managing traumatic brain injury (TBI) patients with a cerebral perfusion pressure (CPP) near to the cerebral autoregulation (CA)-guided “optimal” CPP (CPPopt) value is associated with improved outcome and might be useful to individualize care, but has never been prospectively evaluated.

This study evaluated the feasibility and safety of CA-guided CPP management in TBI patients requiring intracranial pressure monitoring and therapy (TBIicp patients).

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Brain Injury in COVID-19 is Associated with Autoinflammation and Autoimmunity

Publication: Medrxiv

EJ Needham, AL Ren, RJ Digby, JG Outtrim, DA Chatfield, AE Manktelow, VFJ Newcombe, R Doffinger, G Barcenas-Morales, C Fonseca, MJ Taussig, RM Burnstein, C Dunai, N Sithole, NJ Ashton, H Zetterberg, M Gisslen, A Edén, E Marklund, MJ Griffiths, J Cavanagh, G Breen,  View ORCID ProfileSR Irani, A Elmer, N Kingston, JR Bradley, LS Taams,  View ORCID ProfileBD Michael, ET Bullmore, KGC Smith, PA Lyons, AJC Coles, DK Menon, the Cambridge Neuro COVID Group, the NIHR COVID-19 BioResource, Cambridge NIHR Clinical Research Facility

5 December 2021

Summary

COVID-19 has been associated with many neurological complications including stroke, delirium and encephalitis. But it is unknown the full neurological injury Covid-19 has caused.

Researchers investigated the dynamics of, and relationship between, serum markers of brain injury and markers of dysregulated host response including measures of autoinflammation (proinflammatory cytokines) and autoimmunity.

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