About

Deborah Jean Culley, MD, is a Professor of Anesthesiology and Critical Care at the University of Pennsylvania's Perelman School of Medicine. She is part of the Department of Anesthesiology and Critical Care. Her educational background includes an AS from Olympic College in 1985, a BS in Microbiology and Immunology from the University of Washington in 1988, and an MD from the University of Washington School of Medicine in 1992. Her professional focus involves research related to anesthesia, critical care, and postoperative outcomes, with particular attention to delirium, cognitive impairment, and immune neuromodulation in aged populations. Dr. Culley's work includes investigating the effects of anesthesia on immune function and behavior, as well as the perioperative factors associated with adverse outcomes in older patients.

Research topics

• Medicine
• Anesthesia
• Medical education
• Family medicine
• Internal medicine

Selected publications

• Neurologic Disease and Anesthesia

  Elsevier eBooks · 2024-04-05 · 1 citations

  book-chapter
  PublisherDOI

• Contributors

  Elsevier eBooks · 2024-04-05

  book-chapter
  PublisherDOI

• Anesthesiology

  Anesthesiology · 2024-01-05

  articleOpen access
  PublisherOA PDFDOI

• Journal-related Activities and Other Special Activities at the 2024 American Society of Anesthesiologists Meeting

  Anesthesiology · 2024-09-09

  article

  As in previous years, Anesthesiology will sponsor several sessions at the annual meeting of the American Society of Anesthesiologists (ASA), ANESTHESIOLOGY® 2024. The meeting is being held in Philadelphia, Pennsylvania. Details about the format and meeting attendance can be found on the website, asahq.org/annualmeeting. Secrets of Successful Manuscript Preparation, from the Editors of Anesthesiology Saturday, October 19, 2024, 9:45 to 10:45am Room 119AB The editors of Anesthesiology have organized this session to inform authors how to write and prepare a manuscript by providing a clear understanding of what is expected of both research that is considered the best and the manuscript describing it. The goal is to help authors create the best clinical and basic science research for publication. Reviewers will also benefit from this session by learning how to identify key aspects of the best clinical and basic science research. Moderator Michael J. Avram, Ph.D., Assistant Editor-in-Chief, Anesthesiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois Speakers Introduction: Secrets of Successful Manuscript Preparation James P. Rathmell, M.D., M.B.A., Editor-in-Chief, Anesthesiology, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts A Primer on Study Design, Analysis, and Interpretation Subhash Aryal, Ph.D. Statistical Editor, Anesthesiology, Johns Hopkins University, Baltimore, Maryland Snehalata V. Huzurbazar, Ph.D., Statistical Editor, Anesthesiology, Emory University, Atlanta, Georgia How to Prepare an Original Research Manuscript Andrew Davidson, M.B.B.S., M.D., Executive Editor, Anesthesiology, Royal Children’s Hospital and Murdoch Children’s Research Institute, Victoria, Australia How to Write a Review Article and a Few Tips on What Not to Do Deborah J. Culley, M.D., Executive Editor, Anesthesiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania Initial Results: Major Clinical Trials Saturday, October 19, 2024, 11:00amto 12:00pm Room 119AB Anesthesiology is sponsoring its ninth major clinical trials session, a high-profile, large-audience forum for initial presentations of results of major randomized clinical trials. It is designed for substantial trials, usually randomized and blinded, with clinically important primary outcomes. Moderators James P. Rathmell, M.D., M.B.A., Editor-in-Chief, Anesthesiology, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts; Marcos F. Vidal Melo, M.D., Ph.D., Associate Editor, Anesthesiology, Columbia University Irving Medical Center, New York, New York Understanding and Addressing the Anesthesia Workforce Supply and Demand Imbalance Saturday, October 19, 2024, 1:30 to 2:30pm Room 119AB This session, a collaboration between Anesthesiology and ASA Workforce Summit participants, will feature a panel discussion of workforce trends and potential solutions to the workforce challenges faced by the field of anesthesiology. Moderators James P. Rathmell, M.D., M.B.A., Editor-in-Chief, Anesthesiology, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts.; Daniel J. Cole, M.D., University of California Los Angeles, Los Angeles, California Speakers Background Mary Dale Peterson, M.D., M.S.H.C.A., Chair, Task Force on Workforce; ASA Past President; Executive Vice President and Chief Operating Officer, Driscoll Children’s Health; Associate Clinical Professor, Texas A&M University, College Station, Texas Impact on Academic Anesthesiology Seun Johnson Akeju, M.D., Massachusetts General Hospital, Boston, Massachusetts Practice Management and Alternative Models Amr Abouleish, M.D., M.B.A., University of Texas Medical Branch, Galveston, Texas The Promise of Technology Maxime Cannesson, M.D., Ph.D., University of California Los Angeles, Los Angeles, California The Way Forward Thomas R. Miller, Ph.D., M.B.A., American Society of Anesthesiologists, Schaumburg, Illinois Best Abstracts Sunday, October 20, 2024, 8:00 to 11:00am Room 118BC Hosted by Anesthesiology, the Best Abstract session features presentations of both clinical and basic science. The abstracts presented at this session are selected by a panel of editors who examined the highest-scoring abstracts from the ASA subcommittees, choosing those with important scientific and clinical application and novelty. The following are summaries of the excellent abstracts that will be presented. Moderators Michael J. Avram, Ph.D. (lead), Assistant Editor-in-Chief, Anesthesiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois; James P. Rathmell, M.D., M.B.A., Editor-in-Chief, Anesthesiology, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts; Brian T. Bateman, M.D., M.Sc., Editor, Anesthesiology, Stanford Medicine, Stanford, California; Deborah J. Culley, M.D., Executive Editor, Anesthesiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Laszlo Vutskits, M.D., Ph.D., Executive Editor, Anesthesiology, University Hospital of Geneva, Geneva, Switzerland 8520 “Comparative Efficacy of Erector Spinae Plane Block versus Pectointercostal Fascial Plane Block versus Control in Mitigating Postoperative Opioid Requirements following Median Sternotomy: A Prospective, Randomized Controlled Trial” by Daniel Qian, B.A.1, John Choi, D.O.1, Eleonora Koshchak, D.O.1, Shenghao Fang, M.D.1, Yuxia Ouyang, Ph.D.2, Natalia Egorova, Ph.D.2, Ali Shariat, M.D.1, Himani Bhatt-Verma, D.O.1 1Department of Anesthesiology, Perioperative and Pain Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; 2Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York Uncontrolled postoperative pain from sternotomy may lead to the development of chronic pain syndromes. This randomized controlled trial compared the postoperative analgesic efficacy of the bilateral erector spinae plane block and the bilateral pectointercostal fascial plane block to conventional management in 225 patients undergoing cardiac procedures via median sternotomy. Opioid consumption in mg IV morphine equivalents, the primary outcome, was less in the erector spinae plane block and pectointercostal fascial plane block groups than in the control group on postoperative day 3, but there were no differences in this outcome among the groups on postoperative days 0, 1, 2, 4, and 5. 7682 “Hospital- and Clinician-level Differences in Hemodynamic and Resuscitation Practices during Cardiac Surgery and Postoperative Acute Kidney Injury” by Michael Mathis, M.D.1, Graciela Mentz, Ph.D.2, Jie Cao, M.P.H.2, Emily Balczewski, B.A.2, Allison Janda, M.D.1, Donald S. Likosky, Ph.D.3, Robert B. Schonberger, M.D., M.S.4, Sachin Kheterpal, M.D., M.B.A.1, Karandeep Singh, M.D., M.S.5 1Department of Anesthesiology, University of Michigan Medicine, Ann Arbor, Michigan; 2University of Michigan Medicine, Ann Arbor, Michigan; 3Department of Cardiac Surgery, University of Michigan Medicine, Ann Arbor, Michigan; 4Yale School of Medicine, New Haven, Connecticut, 5Department of Medicine, University of California San Diego, San Diego, California Acute kidney injury is commonly observed after cardiac surgery. This observational cohort study sought to quantify clinician- and institution-level intraoperative anesthesia practice variation for cardiac surgery and associations with acute kidney injury. It reviewed 24,726 adult cardiac surgery cases across 202 anesthesiologists and 8 geographically diverse hospitals from 2014 to 2022. Acute kidney injury stage 1 or higher was observed in 5,220 (21.1%) of the cases studied. Adjusted for patient and perioperative characteristics, acute kidney injury was higher for patients at institutions with high inotrope use and low fluid administration and among clinicians with low transfusion rates. 8080 “RBC Transfusion Reduces the Probability of Acute Kidney Injury in Complex Cardiac Surgery: A Phase III Study of Pathogen-Reduced RBCs” by Ronald Pearl, M.D., Ph.D.1, Michael E. Sekela, M.D.2, Edward L. Snyder, M.D.3, Ian J. Welsby, M.B.B.S.4, John McNeil, M.D.5, Gregory A. Nuttall, M.D.6, Kathy Liu, Ph.D.7, Laurence Corash, M.D.7, Nina Mufti, Ph.D.7, Richard J. Benjamin, M.D., Ph.D.7 1Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, California; 2Gill Heart Institute, University of Kentucky, Lexington, Kentucky; 3Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut; 4Anesthesiology and Critical Care, Duke University Medical Center, Durham, North Carolina; 5Anesthesiology, University of Virginia Health System, Charlottesville, Virginia; 6Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota; 7Cerus Corporation, Concord, California The Red Cell Pathogen Inactivation (ReCePI) study was a randomized controlled noninferiority study of 581 patients undergoing complex cardiovascular surgery who were randomized to receive either conventional or pathogen-reduced erythrocyte transfusions. Overall, 55% received erythrocyte transfusions. This subanalysis examined the rate of acute kidney injury, defined as increased serum creatinine from baseline within 48 h of surgery, in transfused versus nontransfused patients. Bayesian analysis including significant covariates confirmed that erythrocyte transfusion was superior to nontransfusion in decreasing the likelihood of acute kidney injury, with an odds ratio of 0.58 and a Bayesian probability of 96.7%. 8447 “Incidence and Outcomes of Perioperative Pulmonary Aspiration: A Retrospective Analysis of 1.6 Million Procedures” by Marta Dias Vaz, M.D.1, Anne Rüggeberg, M.D.2, Edward Bittner, M.D., Ph.D.3, Peter Frykholm, M.D., Ph.D.4, Ashish Khanna, M.D.5, Federico Bilotta, M.D., Ph.D.6, Marcos Vidal Melo, M.D., Ph.D.7, Girish Joshi, M.D., M.B.8, Daniel Sessler, M.D.9, Alexander Nagrebetsky, M.D., M.Sc.3 1Unidade Local de Saúde Gaia e Espinho, V. N. Gaia, Portugal; 2Helios Klinikum Emil von Behring, Berlin, Germany; 3Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts; 4Uppsala University Hospital, Uppsala, Sweden; 5Wake Forest University School of Medicine, Winston Salem, North Carolina; 6Sapienza University of Rome, Rome, Italy; 7Columbia University Irving Medical Center, New York, New York; 8University of Texas Southwestern Medical Center, Dallas, Texas; 9Cleveland Clinic, Cleveland, Ohio This retrospective analysis of elective, urgent, and emergent anesthesia cases in adult and pediatric patients between September 2016 and September 2023 was conducted to quantify the incidence and severity of perioperative pulmonary aspiration. Among 1,626,251 anesthetics performed, 162 cases of suspected perioperative pulmonary aspiration were identified, of which 106 (65%) were classified as highly likely aspirations. Of suspected aspirations, 95 (59%) occurred during elective procedures, 49 (30%) occurred during urgent procedures, and 18 (11%) occurred during emergent procedures. In total, 113 (70%) cases had mild-to-moderate clinical courses, and 49 (30%) were severe. 8411 “The Prevalence of Point-of-Care Ultrasound Abnormalities and Raised Serum B-type Natriuretic Peptide Values in Early Onset Pre-eclampsia” by Raffaella Fantin, M.D.1, Francois Uys, M.D.2, Thomas Schuetz, M.D.3, Margot Flint, Ph.D.2, Carl Lombard, Ph.D.4, Mushi Matjila, M.D.5, Ayesha Osman, M.D.5, Justiaan Swanevelder, M.D.2, Robert Dyer, Ph.D.2, Clemens Ortner, M.D., M.Sc.6 1Department for Anesthesiology and Intensive Care Medicine, Medical University of Innsbruck, Innsbruck, Austria; 2Department of Anesthesia and Perioperative Medicine, University of Cape Town, Cape Town, South Africa; 3Department of Internal Medicine III–Cardiology and Angiology, Medical University of Innsbruck, Innsbruck, Austria; 4Biostatistics Unit, South African Medical Research Council, Cape Town, South Africa; 5Department of Obstetrics and Gynaecology, University of Cape Town, Cape Town, South Africa; 6Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Palo Alto, California This prospective cohort study compared the prevalences of point-of-care ultrasound abnormalities in 65 women with early onset pre-eclampsia with severe features to those reported in women with late onset pre-eclampsia. At least one point-of-care ultrasound abnormality was present in 90% of women. The prevalences of systolic dysfunction, diastolic dysfunction, and increased left ventricular end diastolic pressures (LVEDPs) were higher than in patients with late onset pre-eclampsia. Pulmonary interstitial syndrome was found in 15 of 64 patients. There was no association between pulmonary interstitial syndrome and LVEDP. B-type natriuretic peptide concentrations were associated with the presence of pulmonary interstitial syndrome but not with systolic dysfunction, diastolic dysfunction, or LVEDP. 7394 “The Association between Intraoperative Ketamine Administration and Postoperative Delirium” by Lars Kaiser, Student, Luca Johann Wachtendorf, M.D., Bela-Simon Paschold, M.D., Max Hentges, B.Sc., Elena Ahrens, Student, Ricardo Munoz-Acuna, M.D., Theresa Tenge, M.D., Simone Redaelli, M.D., Victor Novack, M.D., Ph.D., Haobo Ma, M.D., M.S., M.P.H., Maximilian S. Schaefer, M.D., Ph.D. Beth Israel Deaconess Medical Center, Boston, Massachusetts Postoperative pain and disturbances in perception are among several triggers of postoperative delirium. The hypothesis that intraoperative ketamine administration is associated with differential risks of postoperative delirium was tested in a retrospective cohort study of 108,340 patients who underwent noncardiac, non-neurosurgical procedures under general anesthesia between 2008 and 2024. Postoperative delirium developed in 3,138 (2.9%) patients, 329 (2.6%) of whom received intraoperative ketamine. The median (interquartile range) intraoperative ketamine dose was 0.36 (0.25 to 0.52) mg/kg. In adjusted analysis, there was a lower risk of postoperative delirium in patients receiving ketamine, but this association was only in patients who received ketamine. between as by a and Postoperative after Cardiac by M.D., A. Ph.D.2, R. M.D., management Johns Hopkins University School of Medicine, Baltimore, 2Department of Johns Hopkins School of Baltimore, of General Internal Medicine, of Medicine, Johns Hopkins University School of Medicine, Baltimore, of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland on and was developed to identify pressures the of during cardiac surgery that are associated with postoperative delirium. The hypothesis that increased and under the the lower of be associated with postoperative delirium was from prospective and retrospective The incidence of delirium was of in the prospective cohort and of in the retrospective and under the of the lower of were associated with increased odds of postoperative delirium in the retrospective by Analysis of a of Postoperative in by B.A.1, S. M.D., Ph.D.3, Ph.D.4, L. M.D., 1Department of Anesthesia and Perioperative Care, University of San San California; and Center, of University of San San California; 3Department of Anesthesiology, Columbia University Medical New York Hospital, New York, New York; of Anesthesiology and Intensive Care, University of School of Medicine, and intraoperative are of postoperative delirium. This study from a cohort of patients 65 and who underwent surgery to by analysis of the is a of postoperative delirium in In the of the patients had during surgery, the of which was with postoperative delirium had a higher incidence of than those postoperative delirium in to a higher incidence of during of anesthesia of a Perioperative for Major Postoperative by M.D., Ph.D.2, M.D.2, Maxime Cannesson, M.D., Ph.D.2, N. 1Department of Medicine, University of Los Angeles, Los Angeles, California; 2Department of Anesthesiology and Perioperative Medicine, University of Los Angeles, Los Angeles, California; 3Department of Medicine, of University of Los Angeles, Los Angeles, California to postoperative may be to the to identify and major postoperative This study developed and a learning to identify patients at risk of major postoperative after major surgery. considered major and of which developed major postoperative and intraoperative features were to to major postoperative The was the best A both and intraoperative features had an under the of Clinical of for of in to by M.D., Ph.D.1, M.D.1, Ph.D.1, M.D.2, Ph.D.3, Ph.D.1, M.D., New University Hospital, and and block in and and This randomized clinical trial for and block in less than who or block with either or The trial had on in no dose were In of block was in those with than in those with there was no for of Phase Trials of a Pain for of Acute Pain after or by M.D.1, M.D.2, M.D.3, M.D.5, M.D.6, M.D.7, M.D.9, M.D.9, M.D.9, M.D.9, M.D., Clinical Texas; for Medical Atlanta, Texas; Research Center, San California; 8University of California San Diego, California; Boston, Massachusetts; and Women’s Hospital, Boston, Massachusetts is an that is a and highly of with no trials for 48 h in with to severe acute pain after or were randomized to or with had higher of the pain as on the pain from to 48 h than those with but not those with of Intraoperative from by Ph.D. Perioperative Medicine, of Health Clinical Center, Maryland in after injury were examined to the and as of the The major after in patients undergoing with a than h were and in with a on at h or in as and as major by in and differences between and those observed in Pain an for Analysis of Pain and in by B.A.1, Alexander Ph.D.2, Ph.D.1, M.D., Ph.D.3, Ph.D.2, Gregory 1Department of of Perelman School of Medicine, University of Philadelphia, Pennsylvania; 2Department of Institute, University, Pennsylvania; 3Department of and Stanford University, Stanford, California the of in the of pain that be by analgesic efficacy Pain was developed to associated with the of pain in It to the of and from a that morphine and in As with of pain in with acute and chronic pain in the for the of Opioid by Ph.D.1, Ph.D.1, Michael M.D., Ph.D.1, Ph.D.2, M.D., Ph.D.1, 1Department of University of School of Medicine, Pennsylvania; University, Pennsylvania; 3Department of Anesthesiology and Perioperative Medicine, University of School of Medicine, Pennsylvania The and its are in and from the The is a in the of pain and is in The study sought to identify the in the development of a of and in which is for development of several key The to the of A to of of after by M.D.1, B.A.2, F. Ph.D.2, 1Department of Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts; General Hospital, Boston, Massachusetts the of of perioperative to be across were to the learning an that a The of after receiving of ketamine, and to were the learning was defined as learning trials with from and was but were observed after and ketamine. Pulmonary by John M.D., Ph.D., M.D., Ph.D. University of California Los Angeles, Los Angeles, California of the to pulmonary pressures can lead to ventricular The hypothesis that of to ventricular and in pulmonary and of can pulmonary ventricular and ventricular was tested in with pulmonary and ventricular analysis of in the of including of administration of either or in with pulmonary and ventricular ventricular and ventricular New a of than in by M.D., M.D., M.D., M.D., of Anesthesiology, University School of Medicine, There are no that of the to after may be an The of of a dose of was compared with that of a dose of in in the were and The of and to 95 to block of were and The of of at this dose was and that of was for of and the by M.D., Ph.D. Hospital Heart is by a of the with and A of with in of and injury The of the to cardiac and and the were in with ventricular and ventricular and in The to of in to a of cardiac and Anesthesiology in to Sunday, October 20, 2024, 11:00amto 12:00pm Room 119AB The editors of Anesthesiology have organized this session to an of of the significant in the in the Moderator Michael J. Avram, Ph.D., Assistant Editor-in-Chief, Anesthesiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois Speakers James P. Rathmell, M.D., M.B.A., Editor-in-Chief, Anesthesiology, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts; L. M.D., Ph.D., Editor, Anesthesiology, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts and in Anesthesiology Sunday, October 20, 2024, 1:30 to Room 118BC Anesthesiology is sponsoring its annual which will the use of and in anesthesiology. will an of key clinical and research. The session will also feature several presentations of research in this Moderators Sachin Kheterpal, M.D., M.B.A., Editor, Anesthesiology, University of Michigan Medical School, Ann Arbor, Michigan; J. M.D., Editor, Anesthesiology, University of San School of Medicine and the Medical Center, San California Speakers Models in Research and Clinical Practice Gregory J. M.D., Medical Virginia in Hemodynamic Management Maxime Cannesson, M.D., Ph.D., University of California Los Angeles, Los Angeles, California and Models M.D., Ph.D., Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts and of in M.D., Ph.D., University of California San San California Models for Postoperative Outcomes in with Cardiac in the by M.D., M.D.2, M.D., School of Medicine, Virginia; Clinic, to Postoperative Delirium” by M.D., Ph.D., Ricardo Munoz-Acuna, M.D., Haobo Ma, M.D., Maximilian Schaefer, M.D., Ph.D. Beth Israel Deaconess Medical Center, Boston, Massachusetts Models for Perioperative in by M.D.1, M.D., Ph.D.1, and Critical Care Medicine, University School of Medicine and Health University, in the Operating a for by M.D.1, B.A.2, E. M.D., 1Department of Anesthesiology, of University of Minnesota; of University of in Anesthesia for Analysis on the of on Perioperative by M.D.1, M.D., Illinois College of Medicine, Illinois; 2Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California of in by M.D., Ph.D. Hospital for for a Transfusion Clinical by M.D., Ph.D.1, M.D.1, M.D.1, M.D., Ph.D.2, Ronald M.D., Ph.D.3, Ph.D.4, 1Department of Anesthesiology, University in 2Department of Surgery, University in 3Department of and University in of Medicine, University in and of and for about by Donald M.D., M.D., James M.D., Medical Center, Los Angeles, California of and for Postoperative Opioid by M.D., Ph.D.2, Edward M.D., S. M.D., Ph.D.1, M.D., University School of Medicine, Palo Alto, California; Palo Health Care System, Palo Alto, California; University School of Medicine, Palo Alto, California; of Palo Health Care System, Palo Alto, California of Research October 2024, to Room 119AB Hosted by Anesthesiology, the American Society of Anesthesiologists in Research and the James E. M.D., will be presented at the of will present on research The for Anesthesia and Research in Research and the of the American Society of Anesthesiologists Research will be There will be a on for Anesthesia and Research Moderator James P. Rathmell, M.D., M.B.A., Editor-in-Chief, Anesthesiology, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts in The of October 2024, 1:30 to Room 119AB The management in perioperative the and during is this associated with in cases of and a major the administration of can and the management to outcomes. This session, which is by Anesthesiology, will research to management in the with a on the of for and of to the or of patient versus with or and potential research Moderators M.D., Ph.D., Editor, Anesthesiology, Medical School at Texas; J. M.B.A., Editor-in-Chief, Anesthesia University of Speakers the for in Management J. M.B.A., Editor-in-Chief, Anesthesia University of after but the in the of A. M.D., University of Texas Center, Texas in the of What a M.D., Ph.D., Medical University, How the Management of the Thomas M.D., and University of Switzerland with and N. M.D., Hospital, Do in the of B. M.D., University of

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• Microglia in the aged brain develop a hypoactive molecular phenotype after surgery

  Journal of Neuroinflammation · 2024-12-18 · 3 citations

  articleOpen access

  Microglia, the resident immune cells of the brain, play a crucial role in maintaining homeostasis in the central nervous system (CNS). However, they can also contribute to neurodegeneration through their pro-inflammatory properties and phagocytic functions. Acute post-operative cognitive deficits have been associated with inflammation, and microglia have been implicated primarily based on morphological changes. We investigated the impact of surgery on the microglial transcriptome to test the hypothesis that surgery produces an age-dependent pro-inflammatory phenotype in these cells. Three-to-five and 20-to-22-month-old C57BL/6 mice were anesthetized with isoflurane for an abdominal laparotomy, followed by sacrifice either 6 or 48 h post-surgery. Age-matched controls were exposed to carrier gas. Cytokine concentrations in plasma and brain tissue were evaluated using enzyme-linked immunosorbent assays (ELISA). Iba1+ cell density and morphology were determined by immunohistochemistry. Microglia from both surgically treated mice and age-matched controls were isolated by a well-established fluorescence-activated cell sorting (FACS) protocol. The microglial transcriptome was then analyzed using quantitative polymerase chain reaction (qPCR) and RNA sequencing (RNAseq). Surgery induced an elevation in plasma cytokines in both age groups. Notably, increased CCL2 was observed in the brain post-surgery, with a greater change in old compared to young mice. Age, rather than the surgical procedure, increased Iba1 immunoreactivity and the number of Iba1+ cells in the hippocampus. Both qPCR and RNAseq analysis demonstrated suppression of neuroinflammation at 6 h after surgery in microglia isolated from aged mice. A comparative analysis of differentially expressed genes (DEGs) with previously published neurodegenerative microglia phenotype (MGnD), also referred to disease-associated microglia (DAM), revealed that surgery upregulates genes typically downregulated in the context of neurodegenerative diseases. These surgery-induced changes resolved by 48 h post-surgery and only a few DEGs were detected at that time point, indicating that the hypoactive phenotype of microglia is transient. While anesthesia and surgery induce pro-inflammatory changes in the plasma and brain of mice, microglia adopt a homeostatic molecular phenotype following surgery. This effect seems to be more pronounced in aged mice and is transient. These results challenge the prevailing assumption that surgery activates microglia in the aged brain.

  PublisherOA PDFDOI

• Anesthesiology

  Anesthesiology · 2024-02-12

  articleOpen access
  PublisherOA PDFDOI

• Anesthesiology

  Anesthesiology · 2023-09-07

  articleOpen access1st authorCorresponding
  PublisherOA PDFDOI

• Anesthesiology

  Anesthesiology · 2023-08-08

  articleOpen access1st authorCorresponding
  PublisherOA PDFDOI

• Anesthesiology

  Anesthesiology · 2023-12-07

  articleOpen access
  PublisherOA PDFDOI

• Anesthetics inhibit phosphorylation of the ribosomal protein S6 in mouse cultured cortical cells and developing brain

  Frontiers in Aging Neuroscience · 2023-05-16 · 3 citations

  articleOpen access

  Introduction The development and maintenance of neural circuits is highly sensitive to neural activity. General anesthetics have profound effects on neural activity and, as such, there is concern that these agents may alter cellular integrity and interfere with brain wiring, such as when exposure occurs during the vulnerable period of brain development. Under those conditions, exposure to anesthetics in clinical use today causes changes in synaptic strength and number, widespread apoptosis, and long-lasting cognitive impairment in a variety of animal models. Remarkably, most anesthetics produce these effects despite having differing receptor mechanisms of action. We hypothesized that anesthetic agents mediate these effects by inducing a shared signaling pathway. Methods We exposed cultured cortical cells to propofol, etomidate, or dexmedetomidine and assessed the protein levels of dozens of signaling molecules and post-translational modifications using reverse phase protein arrays. To probe the role of neural activity, we performed separate control experiments to alter neural activity with non-anesthetics. Having identified anesthetic-induced changes in vitro , we investigated expression of the target proteins in the cortex of sevoflurane anesthetized postnatal day 7 mice by Western blotting. Results All the anesthetic agents tested in vitro reduced phosphorylation of the ribosomal protein S6, an important member of the mTOR signaling pathway. We found a comparable decrease in cortical S6 phosphorylation by Western blotting in sevoflurane anesthetized neonatal mice. Using a systems approach, we determined that propofol, etomidate, dexmedetomidine, and APV/TTX all similarly modulate a signaling module that includes pS6 and other cell mediators of the mTOR-signaling pathway. Discussion Reduction in S6 phosphorylation and subsequent suppression of the mTOR pathway may be a common and novel signaling event that mediates the impact of general anesthetics on neural circuit development.

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Recent grants

• NIH Grant K08GM077057

  NIH · $724k · 2011

• Preoperative Cognitive Screening in Elderly Surgical Patients: Feasibility and Utility for Predicting Morbidity

  NIH · $506k · 2015–2017

• Preoperative cognitive impairment and adverse geriatric surgical outcomes: role of dysfunctional immunity

  NIH · $759k · 2018–2019

Frequent coauthors

• Gregory Crosby

  Brigham and Women's Hospital

  262 shared

• Michael J. Avram

  Northwestern University

  176 shared

• Evan D. Kharasch

  Duke University

  166 shared

• Jerrold H. Levy

  Duke University

  144 shared

• Zhongcong Xie

  Massachusetts General Hospital

  141 shared

• James P. Rathmell

  Brigham and Women's Hospital

  120 shared

• James C. Eisenach

  Wake Forest University

  108 shared

• Leslie C. Jameson

  88 shared

Education

• Residency, Anesthesiology

  Massachusetts General Hospital

  1996

• Internship, Medicine

  Virginia Mason Medical Center

  1993

• MD, School of Medicine

  University of Washington

  1992

• BS, Microbiology and Immunology

  University of Washington

  1988