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- Li, L. M., et al.
(författare)
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Investigating the characteristics and correlates of systemic inflammation after traumatic brain injury: the TBI-BraINFLAMM study
- 2023
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Ingår i: Bmj Open. - 2044-6055. ; 13:5
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionA significant environmental risk factor for neurodegenerative disease is traumatic brain injury (TBI). However, it is not clear how TBI results in ongoing chronic neurodegeneration. Animal studies show that systemic inflammation is signalled to the brain. This can result in sustained and aggressive microglial activation, which in turn is associated with widespread neurodegeneration. We aim to evaluate systemic inflammation as a mediator of ongoing neurodegeneration after TBI.Methods and analysisTBI-braINFLAMM will combine data already collected from two large prospective TBI studies. The CREACTIVE study, a broad consortium which enrolled >8000 patients with TBI to have CT scans and blood samples in the hyperacute period, has data available from 854 patients. The BIO-AX-TBI study recruited 311 patients to have acute CT scans, longitudinal blood samples and longitudinal MRI brain scans. The BIO-AX-TBI study also has data from 102 healthy and 24 non-TBI trauma controls, comprising blood samples (both control groups) and MRI scans (healthy controls only). All blood samples from BIO-AX-TBI and CREACTIVE have already been tested for neuronal injury markers (GFAP, tau and NfL), and CREACTIVE blood samples have been tested for inflammatory cytokines. We will additionally test inflammatory cytokine levels from the already collected longitudinal blood samples in the BIO-AX-TBI study, as well as matched microdialysate and blood samples taken during the acute period from a subgroup of patients with TBI (n=18).We will use this unique dataset to characterise post-TBI systemic inflammation, and its relationships with injury severity and ongoing neurodegeneration.Ethics and disseminationEthical approval for this study has been granted by the London-Camberwell St Giles Research Ethics Committee (17/LO/2066). Results will be submitted for publication in peer-review journals, presented at conferences and inform the design of larger observational and experimental medicine studies assessing the role and management of post-TBI systemic inflammation.
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- Maier, O., et al.
(författare)
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ISLES 2015-A public evaluation benchmark for ischemic stroke lesion segmentation from multispectral MRI
- 2017
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Ingår i: Medical Image Analysis. - : Elsevier BV. - 1361-8415 .- 1361-8423. ; 35, s. 250-269
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Tidskriftsartikel (refereegranskat)abstract
- Ischemic stroke is the most common cerebrovascular disease, and its diagnosis, treatment, and study relies on non-invasive imaging. Algorithms for stroke lesion segmentation from magnetic resonance imaging (MRI) volumes are intensely researched, but the reported results are largely incomparable due to different datasets and evaluation schemes. We approached this urgent problem of comparability with the Ischemic Stroke Lesion Segmentation (ISLES) challenge organized in conjunction with the MICCAI 2015 conference. In this paper we propose a common evaluation framework, describe the publicly available datasets, and present the results of the two sub-challenges: Sub-Acute Stroke Lesion Segmentation (SISS) and Stroke Perfusion Estimation (SPES). A total of 16 research groups participated with a wide range of state-of-the-art automatic segmentation algorithms. A thorough analysis of the obtained data enables a critical evaluation of the current state-of-the-art, recommendations for further developments, and the identification of remaining challenges. The segmentation of acute perfusion lesions addressed in SPES was found to be feasible. However, algorithms applied to sub-acute lesion segmentation in SISS still lack accuracy. Overall, no algorithmic characteristic of any method was found to perform superior to the others. Instead, the characteristics of stroke lesion appearances, their evolution, and the observed challenges should be studied in detail. The annotated ISLES image datasets continue to be publicly available through an online evaluation system to serve as an ongoing benchmarking resource (www.isles-challenge.org).
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- Menard, S, et al.
(författare)
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Developmental switch of intestinal antimicrobial peptide expression
- 2008
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 205:1, s. 183-193
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Tidskriftsartikel (refereegranskat)abstract
- Paneth cell–derived enteric antimicrobial peptides provide protection from intestinal infection and maintenance of enteric homeostasis. Paneth cells, however, evolve only after the neonatal period, and the antimicrobial mechanisms that protect the newborn intestine are ill defined. Using quantitative reverse transcription–polymerase chain reaction, immunohistology, reverse-phase high-performance liquid chromatography, and mass spectrometry, we analyzed the antimicrobial repertoire in intestinal epithelial cells during postnatal development. Surprisingly, constitutive expression of the cathelin-related antimicrobial peptide (CRAMP) was observed, and the processed, antimicrobially active form was identified in neonatal epithelium. Peptide synthesis was limited to the first two weeks after birth and gradually disappeared with the onset of increased stem cell proliferation and epithelial cell migration along the crypt–villus axis. CRAMP conferred significant protection from intestinal bacterial growth of the newborn enteric pathogen Listeria monocytogenes. Thus, we describe the first example of a complete developmental switch in innate immune effector expression and anatomical distribution. Epithelial CRAMP expression might contribute to bacterial colonization and the establishment of gut homeostasis, and provide protection from enteric infection during the postnatal period.
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- Newcombe, Virginia F J, et al.
(författare)
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Post-acute blood biomarkers and disease progression in traumatic brain injury.
- 2022
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 145:6, s. 2064-2076
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Tidskriftsartikel (refereegranskat)abstract
- There is substantial interest in the potential for traumatic brain injury to result in progressive neurological deterioration. While blood biomarkers such as glial fibrillary acid protein and neurofilament light have been widely explored in characterising acute traumatic brain injury, their use in the chronic phase is limited. Given increasing evidence that these proteins may be markers of ongoing neurodegeneration in a range of diseases, we examined their relationship to imaging changes and functional outcome in the months to years following traumatic brain injury. Two-hundred and three patients were recruited in two separate cohorts; six months post-injury (n=165); and >5 years post-injury (n=38; 12 of whom also provided data ∼8 months post-TBI). Subjects underwent blood biomarker sampling (n=199) and magnetic resonance imaging (n=172; including diffusion tensor imaging). Data from patient cohorts were compared to 59 healthy volunteers and 21 non-brain injury trauma controls. Mean diffusivity and fractional anisotropy were calculated in cortical grey matter, deep grey matter and whole brain white matter. Accelerated brain ageing was calculated at a whole brain level as the predicted age difference defined using T1-weighted images, and at a voxel-based level as the annualised Jacobian determinants in white matter and grey matter, referenced to a population of 652 healthy control subjects. Serum neurofilament light concentrations were elevated in the early chronic phase. While GFAP values were within the normal range at ∼8 months, many patients showed a secondary and temporally distinct elevations up to >5 years after injury. Biomarker elevation at six months was significantly related to metrics of microstructural injury on diffusion tensor imaging. Biomarker levels at ∼8 months predicted white matter volume loss at >5 years, and annualised brain volume loss between ∼8 months and 5 years. Patients who worsened functionally between ∼8 months and >5 years showed higher than predicted brain age and elevated neurofilament light levels. Glial fibrillary acid protein and neurofilament light levels can remain elevated months to years after traumatic brain injury, and show distinct temporal profiles. These elevations correlate closely with microstructural injury in both grey and white matter on contemporaneous quantitative diffusion tensor imaging. Neurofilament light elevations at ∼8 months may predict ongoing white matter and brain volume loss over >5 years of follow up. If confirmed, these findings suggest that blood biomarker levels at late time points could be used to identify traumatic brain injury survivors who are at high risk of progressive neurological damage.
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