Simon T Dillon1,2,3, Hasan H Otu4, Long H Ngo3,5, Tamara G Fong3,6,7, Sarinnapha M Vasunilashorn3,5,8, Zhongcong Xie3,9, Lisa J Kunze3,10, Kamen V Vlassakov3,11, Ayesha Abdeen3,12, Jeffrey K Lange3,13, Brandon E Earp3,14, Zara R Cooper3,15, Eva M Schmitt7, Steven E Arnold16, Tammy T Hshieh3,5,7, Richard N Jones17,18, Sharon K Inouye3,7, Edward R Marcantonio3,5, Towia A Libermann1,2,3. 1. From the Division of Interdisciplinary Medicine and Biotechnology. 2. Genomics, Proteomics, Bioinformatics and Systems Biology Center, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts. 3. Department of Medicine, Harvard Medical School, Boston, Massachusetts. 4. Department of Electrical Engineering, University of Nebraska, Lincoln, Nebraska. 5. Division of General Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts. 6. Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts. 7. Aging Brain Center, Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts. 8. Departments of Epidemiology and Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 9. Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts. 10. Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts. 11. Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts. 12. Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts. 13. Department of Orthopedic Surgery, Brigham and Women's Hospital, Boston, Massachusetts. 14. Department of Orthopedic Surgery, Brigham and Women's Faulkner Hospital, Boston, Massachusetts. 15. Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts. 16. Department of Neurology, Harvard Medical School, Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, Massachusetts; and Departments of. 17. Psychiatry and Human Behavior and. 18. Neurology, Warren Alpert Medical School, Brown University, Providence, Rhode Island.
Abstract
BACKGROUND: The neuroinflammatory response to surgery can be characterized by peripheral acute plasma protein changes in blood, but corresponding, persisting alterations in cerebrospinal fluid (CSF) proteins remain mostly unknown. Using the SOMAscan assay, we define acute and longer-term proteome changes associated with surgery in plasma and CSF. We hypothesized that biological pathways identified by these proteins would be in the categories of neuroinflammation and neuronal function and define neuroinflammatory proteome changes associated with surgery in older patients. METHODS: SOMAscan analyzed 1305 proteins in blood plasma (n = 14) and CSF (n = 15) samples from older patients enrolled in the Role of Inflammation after Surgery for Elders (RISE) study undergoing elective hip and knee replacement surgery with spinal anesthesia. Systems biology analysis identified biological pathways enriched among the surgery-associated differentially expressed proteins in plasma and CSF. RESULTS: Comparison of postoperative day 1 (POD1) to preoperative (PREOP) plasma protein levels identified 343 proteins with postsurgical changes (P < .05; absolute value of the fold change [|FC|] > 1.2). Comparing postoperative 1-month (PO1MO) plasma and CSF with PREOP identified 67 proteins in plasma and 79 proteins in CSF with altered levels (P < .05; |FC| > 1.2). In plasma, 21 proteins, primarily linked to immune response and inflammation, were similarly changed at POD1 and PO1MO. Comparison of plasma to CSF at PO1MO identified 8 shared proteins. Comparison of plasma at POD1 to CSF at PO1MO identified a larger number, 15 proteins in common, most of which are regulated by interleukin-6 (IL-6) or transforming growth factor beta-1 (TGFB1) and linked to the inflammatory response. Of the 79 CSF PO1MO-specific proteins, many are involved in neuronal function and neuroinflammation. CONCLUSIONS: SOMAscan can characterize both short- and long-term surgery-induced protein alterations in plasma and CSF. Acute plasma protein changes at POD1 parallel changes in PO1MO CSF and suggest 15 potential biomarkers for longer-term neuroinflammation that warrant further investigation.
BACKGROUND: The neuroinflammatory response to surgery can be characterized by peripheral acute plasma protein changes in blood, but corresponding, persisting alterations in cerebrospinal fluid (CSF) proteins remain mostly unknown. Using the SOMAscan assay, we define acute and longer-term proteome changes associated with surgery in plasma and CSF. We hypothesized that biological pathways identified by these proteins would be in the categories of neuroinflammation and neuronal function and define neuroinflammatory proteome changes associated with surgery in older patients. METHODS: SOMAscan analyzed 1305 proteins in blood plasma (n = 14) and CSF (n = 15) samples from older patients enrolled in the Role of Inflammation after Surgery for Elders (RISE) study undergoing elective hip and knee replacement surgery with spinal anesthesia. Systems biology analysis identified biological pathways enriched among the surgery-associated differentially expressed proteins in plasma and CSF. RESULTS: Comparison of postoperative day 1 (POD1) to preoperative (PREOP) plasma protein levels identified 343 proteins with postsurgical changes (P < .05; absolute value of the fold change [|FC|] > 1.2). Comparing postoperative 1-month (PO1MO) plasma and CSF with PREOP identified 67 proteins in plasma and 79 proteins in CSF with altered levels (P < .05; |FC| > 1.2). In plasma, 21 proteins, primarily linked to immune response and inflammation, were similarly changed at POD1 and PO1MO. Comparison of plasma to CSF at PO1MO identified 8 shared proteins. Comparison of plasma at POD1 to CSF at PO1MO identified a larger number, 15 proteins in common, most of which are regulated by interleukin-6 (IL-6) or transforming growth factor beta-1 (TGFB1) and linked to the inflammatory response. Of the 79 CSF PO1MO-specific proteins, many are involved in neuronal function and neuroinflammation. CONCLUSIONS: SOMAscan can characterize both short- and long-term surgery-induced protein alterations in plasma and CSF. Acute plasma protein changes at POD1 parallel changes in PO1MO CSF and suggest 15 potential biomarkers for longer-term neuroinflammation that warrant further investigation.
Authors: Vladimir V Senatorov; Aaron R Friedman; Dan Z Milikovsky; Jonathan Ofer; Rotem Saar-Ashkenazy; Adiel Charbash; Naznin Jahan; Gregory Chin; Eszter Mihaly; Jessica M Lin; Harrison J Ramsay; Ariana Moghbel; Marcela K Preininger; Chelsy R Eddings; Helen V Harrison; Rishi Patel; Yishuo Shen; Hana Ghanim; Huanjie Sheng; Ronel Veksler; Peter H Sudmant; Albert Becker; Barry Hart; Michael A Rogawski; Andrew Dillin; Alon Friedman; Daniela Kaufer Journal: Sci Transl Med Date: 2019-12-04 Impact factor: 17.956
Authors: Zoe S Gan; Sherman C Stein; Randel Swanson; Shaobo Guan; Lizette Garcia; Devanshi Mehta; Douglas H Smith Journal: Front Neurol Date: 2019-04-26 Impact factor: 4.003
Authors: Harald Hampel; Filippo Caraci; A Claudio Cuello; Giuseppe Caruso; Robert Nisticò; Massimo Corbo; Filippo Baldacci; Nicola Toschi; Francesco Garaci; Patrizia A Chiesa; Steven R Verdooner; Leyla Akman-Anderson; Félix Hernández; Jesús Ávila; Enzo Emanuele; Pedro L Valenzuela; Alejandro Lucía; Mark Watling; Bruno P Imbimbo; Andrea Vergallo; Simone Lista Journal: Front Immunol Date: 2020-03-31 Impact factor: 7.561