eprintid: 10051423 rev_number: 18 eprint_status: archive userid: 608 dir: disk0/10/05/14/23 datestamp: 2018-07-03 08:57:00 lastmod: 2021-10-24 23:22:51 status_changed: 2018-07-03 08:57:00 type: article metadata_visibility: show creators_name: Fernström, E creators_name: Minta, K creators_name: Andreasson, U creators_name: Sandelius, Å creators_name: Wasling, P creators_name: Brinkmalm, A creators_name: Höglund, K creators_name: Blennow, K creators_name: Nyman, J creators_name: Zetterberg, H creators_name: Kalm, M title: Cerebrospinal fluid markers of extracellular matrix remodelling, synaptic plasticity and neuroinflammation before and after cranial radiotherapy ispublished: inpress divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F86 keywords: CSF biomarkers, cranial irradiation, neuronal damage, small-cell lung cancer note: © 2018 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. abstract: BACKGROUND: Advances in the treatment of brain tumours have increased the number of long-term survivors, but at the cost of side effects following cranial radiotherapy ranging from neurocognitive deficits to outright tissue necrosis. At present, there are no tools reflecting the molecular mechanisms underlying such side effects, and thus no means to evaluate interventional effects after cranial radiotherapy. Therefore, fluid biomarkers are of great clinical interest. OBJECTIVE: Cerebrospinal fluid (CSF) levels of proteins involved in inflammatory signalling, synaptic plasticity and extracellular matrix (ECM) integrity were investigated following radiotherapy to the brain. METHODS: Patients with small-cell lung cancer (SCLC) eligible for prophylactic cranial irradiation (PCI) were asked to participate in the study. PCI was prescribed either as 2 Gy/fraction to a total dose of 30 Gy (limited disease) or 4 Gy/fraction to 20 Gy (extensive disease). CSF was collected by lumbar puncture at baseline, 3 months and 1 year following PCI. Protein concentrations were measured using immunobased assays or mass spectrometry. RESULTS: The inflammatory markers IL-15, IL-16 and MCP-1/CCL2 were elevated in CSF 3 months following PCI compared to baseline. The plasticity marker GAP-43 was elevated 3 months following PCI, and the same trend was seen for SNAP-25, but not for SYT1. The investigated ECM proteins, brevican and neurocan, showed a decline following PCI. There was a strong correlation between the progressive decline of soluble APPα and brevican levels. CONCLUSION: To our knowledge, this is the first time ECM-related proteins have been shown to be affected by cranial radiotherapy in patients with cancer. These findings may help us to get a better understanding of the mechanisms behind side effects following radiotherapy. date: 2018-04-17 date_type: published official_url: http://dx.doi.org/10.1111/joim.12763 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green article_type_text: Journal Article verified: verified_manual elements_id: 1550329 doi: 10.1111/joim.12763 lyricists_name: Zetterberg, Henrik lyricists_id: HZETT94 actors_name: Bracey, Alan actors_id: ABBRA90 actors_role: owner full_text_status: public publication: Journal of Internal Medicine event_location: England issn: 1365-2796 citation: Fernström, E; Minta, K; Andreasson, U; Sandelius, Å; Wasling, P; Brinkmalm, A; Höglund, K; ... Kalm, M; + view all <#> Fernström, E; Minta, K; Andreasson, U; Sandelius, Å; Wasling, P; Brinkmalm, A; Höglund, K; Blennow, K; Nyman, J; Zetterberg, H; Kalm, M; - view fewer <#> (2018) Cerebrospinal fluid markers of extracellular matrix remodelling, synaptic plasticity and neuroinflammation before and after cranial radiotherapy. Journal of Internal Medicine 10.1111/joim.12763 <https://doi.org/10.1111/joim.12763>. (In press). Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10051423/1/Cerebrospinal%20fluid%20and%20blood%20biomarkers%20for%20neurodegenerative%20dementias%20An%20update%20of%20the%20Consensus%20of%20the%20Task%20Force%20on%20Biological%20Markers%20in.pdf