The neuroinflammation group have an interest in central nervous system inflammation following acute brain injuries such as Traumatic Brain Injury (TBI) and Subarachnoid Haemorrhage (SAH). Innate inflammation comprises of a complex sequence of cellular and humoral responses following any neurological insult. These responses can be protective leading to clearance of cellular debris and promoting a reparative environment, but they can also exacerbate neuronal injury. We are a clinically focussed group that aims to determine how neuroinflammatory responses impact on metabolism and how this can be modulated as a therapeutic target.

• Microdialysis Monitoring of Inflammatory Mediators

Microdialysis is an invasive method of sampling the brain extracellular space and is used clinically as a monitoring tool following both TBI and SAH. The same catheters can be used to recover cytokines and chemokines directly from the human brain.

• Clinical Trials of Neuromodulatory Agents

We are actively trialling neuroprotective agents in TBI, to modify the neuroinflammatory cascade and ameliorate the damaging effects of neuroinflammation.

• Statistical Methods

Inflammatory mediators act in complex cascades and their concentrations in the brain are highly correlated: in statistical terms they show high collinearity. Specialised methods for interpreting this data are necessary to determine which mediators are injurious.

• Cellular Drivers of Inflammation

We are actively developing a methodology for extracting and separating single cells from the human brain to investigate the source of the cytokines and chemokines that we detect following acute brain injury.

Group Leader:

Mr Adel Helmy University Associate Professor & Hon Consultant Neurosurgeon Email: aeh33@cam.ac.uk

Members:

Professor Peter Hutchinson

Dr Keri Carpenter

Mr Mathew Guilfoyle

Miss Tamara Tajsic

Dr M. Aftab Alam

Elika Karvandi

Dr Adam Safwat

Collaborators:

Professor David Menon

Professor Stephen Sawcer

Professor Rickie Patani

Professor Menna Clatworthy

Dr Maria Ban

Dr Lori Turner

Dr Gwenael Leday

Previous Members:

Dr Eric Thelin

Abdelhakim Khellaf

Dr Danyal Khan

Dr Agnieszka Zakrzewska

Key Publications

1. Khellaf A, Garcia NM, Tajsic T, Alam A, Stovell MG, Killen MJ, Howe DJ, Guilfoyle MR, Jalloh I, Timofeev I, Murphy MP, Carpenter TA, Menon DK, Ercole A, Hutchinson PJ, Carpenter KL, Thelin EP, Helmy A.Focally administered succinate improves cerebral metabolism in traumatic brain injury patients with mitochondrial dysfunction. J Cereb Blood Flow Metab. 2021 Sep 8:271678X211042112. doi: 10.1177/0271678X211042112.
2. Needham EJ, Stoevesandt O, Thelin EP, Zetterberg H, Zanier ER, Al Nimer F, Ashton NJ, Outtrim JG, Newcombe VFJ, Mousa HS, Simrén J, Blennow K, Yang Z, Hutchinson PJ, Piehl F, Helmy AE, Taussig MJ, Wang KKW, Jones JL, Menon DK, Coles AJ. Complex Autoantibody Responses Occur following Moderate to Severe Traumatic Brain Injury. J Immunol. 2021 Jun 18:ji2001309. doi: 10.4049/jimmunol.2001309.
3. Fitzpatrick Z, Frazer G, Ferro A, Clare S, Bouladoux N, Ferdinand J, Tuong ZK, Negro-Demontel ML, Kumar N, Suchanek O, Tajsic T, Harcourt K, Scott K, Bashford-Rogers R, Helmy A, Reich DS, Belkaid Y, Lawley TD, McGavern DB, Clatworthy MR. Gut-educated IgA plasma cells defend the meningeal venous sinuses. Nature 2020 Nov 4. doi: 10.1038/s41586-020-2886-4.
4. Alam A, Thelin EP, Tajsic T, Khan DZ, Khellaf A, Patani R, Helmy A. Cellular infiltration in traumatic brain injury. J Neuroinflammation. 2020 Nov 3;17(1):328. doi: 10.1186/s12974-020-02005-x.
5. Lauwers E, Lalli G, Brandner S, Collinge J, Compernolle V, Duyckaerts C, Edgren G, Haïk S, Hardy J, Helmy A, Ivinson AJ, Jaunmuktane Z, Jucker M, Knight R, Lemmens R, Lin IC, Love S, Mead S, Perry VH, Pickett J, Poppy G, Radford SE, Rousseau F, Routledge C, Schiavo G, Schymkowitz J, Selkoe DJ, Smith C, Thal DR, Theys T, Tiberghien P, van den Burg P, Vandekerckhove P, Walton C, Zaaijer HL, Zetterberg H, De Strooper B. Potential human transmission of amyloid β pathology: surveillance and risks.Lancet Neurol. 2020 Oct;19(10):872-878
6. Thelin EP, Hall CE, Tyzack GE, Frostell A, Giorgi-Coll S, Alam A, Carpenter K, Mitchell J, Tajsic T, Hutchinson PJ, Patani R, Helmy A. Delineating Astrocytic Cytokine Responses in a Human Stem Cell Model of Neural Trauma. J Neurotrauma. 2019 Aug 27.
7. Agoston V, Vink R, Helmy A, Risling M, Nelson D, Prins M. How to Translate Time: The Temporal Aspects of Rodent and Human Pathobiological Processes in Traumatic Brain Injury. J Neurotrauma. 2019 Mar 7.
8. Tsyben A, Guilfoyle M, Timofeev I, Anwar F, Allanson J, Outtrim J, Menon D, Hutchinson P, Helmy A. Spectrum of outcomes following traumatic brain injury-relationship between functional impairment and health-related quality of life. Acta Neurochir (Wien).  2018 Jan;160(1):107-115.
9. Thelin EP, Hall CE, Gupta K, Carpenter K, Chandran S, Hutchinson PJ, Patani R, Helmy A. Elucidating pro-inflammatory cytokine responses following traumatic brain injury in a human stem cell model. J Neurotrauma. 2017 Oct 5.
10. Jalloh I, Helmy A, Howe DJ, Shannon RJ, Grice P, Mason A, Gallagher CN, Stovell MG, van der Heide S, Murphy MP, Pickard JD, Menon DK, Carpenter TA, Hutchinson PJ, Carpenter KL. Focally perfused succinate potentiates brain metabolism in head injury patients. J Cereb Blood Flow Metab. 2017Jul;37(7):2626-2638.
11. Helmy A, Guilfoyle MR, Carpenter KL, Pickard JD, Menon DK, Hutchinson PJ. Recombinant human interleukin-1 receptor antagonist promotes M1 microglia biased cytokines and chemokines following human traumatic brain injury. J Cereb Blood Flow Metab. 2016 Vol 36(8) 1434-1448
12. Hutchinson PJ, Jalloh I, Helmy A, Carpenter KL, Rostami E, et al.Consensus statement from the 2014 International Microdialysis Forum. Intensive Care Med. 2015 Sep;41(9):1517-28.
13. Guilfoyle MR, Carpenter K, Helmy A, Pickard J, Menon D, Hutchinson PJ. Matrix Metalloproteinase Expression in Contusional Traumatic Brain Injury: A Paired Microdialysis Study. J Neurotrauma. 2015 Oct 15;32(20):1553-9]
14. Budohoski KP, Guilfoyle M, Helmy A, Huuskonen T, Czosnyka M, Kirollos R, Menon DK, Pickard JD, Kirkpatrick PJ.The pathophysiology and treatment of delayed cerebral ischaemia following subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry. 2014 May 20.
15. Helmy A, Guilfoyle MR, Carpenter KL, Pickard JD, Menon DK, Hutchinson PJ. Recombinant Human Interleukin-1 Receptor Antagonist in Severe Traumatic Brain Injury: a Phase II Randomised Control Trial. Journal Cerebral Blood Flow and Metabolism 2014 Feb 26. doi: 10.1038/jcbfm.2014.23.
16. Helmy A, Antoniades CA, Guilfoyle MR, Carpenter KL, Hutchinson PJ. Principal component analysis of the cytokine and chemokine response to human traumatic brain injury. PLoS One. 2012;7(6):e39677. Epub 2012 Jun 22.
17. Helmy A, De Simoni MG, Guilfoyle MR, Carpenter KL, Hutchinson PJ. Cytokines and innate inflammation in the pathogenesis of human traumatic brain injury. Prog Neurobiol. 2011 Nov;95(3):352-72. Epub 2011 Sep 16.
18. Helmy A, Carpenter KL, Menon DK, Pickard JD, Hutchinson PJ. The cytokine response to human traumatic brain injury: temporal profiles and evidence for cerebral parenchymal production. J Cereb Blood Flow Metab. 2010 Aug 18.
19. Helmy A, Carpenter KL, Skepper JN, Kirkpatrick PJ, Pickard JD, Hutchinson PJ. Microdialysis of cytokines: methodological considerations, scanning electron microscopy, and determination of relative recovery. J Neurotrauma. 2009 Apr;26(4):549-61.