Imperial College London

Professor Paul M. Matthews

Faculty of MedicineDepartment of Medicine

Edmond and Lily Safra Chair and Head of Brain Sciences
 
 
 
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Contact

 

+44 (0)20 7594 2855p.matthews

 
 
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Assistant

 

Ms Siobhan Dillon +44 (0)20 7594 2855

 
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Location

 

E502Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Scott:2017:brain/awx339,
author = {Scott, GPT and Zetterberg, H and Jolly, A and Cole, JH and De, Simoni S and Jenkins, PO and Feeney, C and Owen, DR and Lingford-Hughes, A and Howes, O and Patel, MC and Goldstone, AP and Gunn, RN and Blennow, K and Matthews, PM and Sharp, DJ},
doi = {brain/awx339},
journal = {Brain},
pages = {459--471},
title = {Minocycline reduces chronic microglial activation after brain trauma but increases neurodegeneration},
url = {http://dx.doi.org/10.1093/brain/awx339},
volume = {141},
year = {2017}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Survivors of a traumatic brain injury can deteriorate years later, developing brain atrophy and dementia. Traumatic brain injury triggers chronic microglial activation, but it is unclear whether this is harmful or beneficial. A successful chronic-phase treatment for traumatic brain injury might be to target microglia. In experimental models, the antibiotic minocycline inhibits microglial activation. We investigated the effect of minocycline on microglial activation and neurodegeneration using PET, MRI, and measurement of the axonal protein neurofilament light in plasma. Microglial activation was assessed using 11C-PBR28 PET. The relationships of microglial activation to measures of brain injury, and the effects of minocycline on disease progression, were assessed using structural and diffusion MRI, plasma neurofilament light, and cognitive assessment. Fifteen patients at least 6 months after a moderate-to-severe traumatic brain injury received either minocycline 100 mg orally twice daily or no drug, for 12 weeks. At baseline, 11C-PBR28 binding in patients was increased compared to controls in cerebral white matter and thalamus, and plasma neurofilament light levels were elevated. MRI measures of white matter damage were highest in areas of greater 11C-PBR28 binding. Minocycline reduced 11C-PBR28 binding (mean Δwhite matter binding = −23.30%, 95% confidence interval −40.9 to −5.64%, P = 0.018), but increased plasma neurofilament light levels. Faster rates of brain atrophy were found in patients with higher baseline neurofilament light levels. In this experimental medicine study, minocycline after traumatic brain injury reduced chronic microglial activation while increasing a marker of neurodegeneration. These findings suggest that microglial activation has a reparative effect in the chronic phase of traumatic brain injury.
AU - Scott,GPT
AU - Zetterberg,H
AU - Jolly,A
AU - Cole,JH
AU - De,Simoni S
AU - Jenkins,PO
AU - Feeney,C
AU - Owen,DR
AU - Lingford-Hughes,A
AU - Howes,O
AU - Patel,MC
AU - Goldstone,AP
AU - Gunn,RN
AU - Blennow,K
AU - Matthews,PM
AU - Sharp,DJ
DO - brain/awx339
EP - 471
PY - 2017///
SN - 1460-2156
SP - 459
TI - Minocycline reduces chronic microglial activation after brain trauma but increases neurodegeneration
T2 - Brain
UR - http://dx.doi.org/10.1093/brain/awx339
UR - http://hdl.handle.net/10044/1/54179
VL - 141
ER -