Sponsored Lecture 1

Mechanism of perinatal brain injury

Henrik Hagberg
Perinatal Center, Sahlgrenska Academy, Gothenburg, Sweden
Centre for the Developing Brain, Kings College London, London, United Kingdom

Mitochondria are dynamic double-membrane-bound organelles that are involved in a wide range of cellular processes, including ATP
generation, calcium homeostasis, as well as the biosynthesis of amino acids, lipids and nucleotides. They differ with respect to size,
density, ROS production, respiratory/ Ca2 + regulatory activity and substrate preference in the immature compared with adult brain,
suggesting unique control mechanisms in the developing CNS.
Mitochondria are center stage in the regulation of cell death in the immature brain. They control apoptotic, necrotic/necroptotic and
autophagic events after injury and their dynamic properties seems critical for CNS development and maybe also cell fate. Mitochondrial
biogenesis, mitophagy and transcellular exchange can be important for repair processes in several tissues including the CNS. Mitochondria
are also, at least partly, responsible for induction of CNS tolerance in the immature brain. Mitochondria have recently been recognized
as an important scaffold for innate immune responses related to pattern recognition receptor regulation. We propose that mitochondria
are important in both anti-microbial defense as well as triggering of inammation after sterile insults.
Based on this knowledge, mitochondria-directed neuroprotective therapies (Mitoprotectants) such as caspase-2 inhibitors are being
developed to combat injurious events in the immature brain. We found recently that magnesium (Mg) in therapeutic concentrations given
as a bolus dose 12h-3days prior to hypoxia-ischemia (HI) provides marked preconditioning protection. This effects is different compared
with hypoxic preconditioning as it is unrelated to cerebral blood ow during the subsequent HI. We hypothesize that Mg induces
mitoprotection through regulation of mitochondrial Ca2 + uxes, mitochondrial ATP-sensitive K + channels and transient receptor potential
ion channels.
It is reasonable to believe that further insights into these basic and pathological aspects of mitochondria will be of paramount importance
for understanding brain development, neurologic disease and for finding new strategies for treatment.
CURRICULUM VITAE
Henrik Hagberg
Born: March 31, 1955, Stockholm, Sweden, two children
Professional preparation
1979-1985 Medicine doktor, (PhD)
Thesis: Electrolyte, pH and metabolic changes in skeletal muscle during ischemia
Supervisor: Hengo Haljame, PhD, Dept of Neurobiology, Gteborg, Sweden
1987
Registered Physician (Legitimerad lkare)
1976-1985 Lkarexamen (MD), Sahlgrenska Academy, Gteborg, Sweden
Appointments
2012-09 Professor in Perinatology and Obstetrics, Department of Clinical Sciences, Department of Obstetrics and Gynecology,
Sahlgrenska Academy, Gteborg and Professor, Chair in Fetal Medicine, Centre for the Developing Brain, Perinatal
Imaging & Health, Kings College London, London
2010-2012-08 Shared Professorship in Perinatology and Obstetrics, Department of Clinical Sciences, Department of Obstetrics and
Gynecology, Sahlgrenska Academy, Gteborg and Imperial College, Institute of Reproductive and Developmental
Biology, London.
2008-2010
Professor in Obstetrics, Imperial College, Institute of Reproductive and Developmental Biology, Queen Charlottes and
Chelsea Hospital, London
2000-2008
Professor in Perinatal Medicine and Obstetrics, Institute for the Health of Women and Children, Sahlgrenska Academy,
Gteborg University
2000-2001
Guest professor at the Neuroscience Lab, Kennedy Krieger Institute, Johns Hopkins School of Medicine, Baltimore, USA
1995-1999
Associate Professor and senior clinical consultant in Perinatal Medicine and Obstetrics
1993-1995
Assistant Professor (Docent) in Obstetrics and Gynecology, Gteborg and consultant physician at the Dept of Obstetrics
and Gynecology, Sahlgrenska University Hospital
1985Assistant Professorship (Docent) in Neurobiology
1994-1998
Research assistant, Swedish Medical Reasearch Council
1997
Associate Professor, (Docentur; Experimental Medicine)
1991-1993
Consultant in Obstetrics and Gynecology, Gteborg
1987-1991
Residency, Bors hospital, Mlndals hospital and Sahlgrenska University Hospital
1985-1987
Internship (AT-tjnstgring), Mlndals hospital, Mlndal
Commissions of trust
Abstracts for The 46th International Congress on Pathophysiology of Pregnancy

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Commissioned to be opponent at 16 occasions for the following Ph.D. examinations:

Hiroaki Minamisawa, (Lund, 1995); Ping-An Li, (Lund 1996); Lars Gisselsson, (Lund1998); Kersti Haaland, (1999,Oslo); Gregor
Tomasevic, (Lund 1999); Cacha Peeters-Scholte, (Utrecht 1999); Jhodie Duncan, (Melbourne, AUS, 2000); Kristina Thorngren-Jerneck,
(Lund 2002); Stefan Kutzsche, (Oslo 2002); Bhatia Inderjeet, (Hong Kong 2003); Evylin van den Tweel, (Utrecht 2004); Nasim
Farrokhina (Uppsala 2005); Charlotte Israelsson (Uppsala 2006); Eva Wiberg-Itzel, (Stockholm 2007); Barbara Botallico, (Lund 2007);
Elisabeth Fryland, (Oslo 2008) External Examiner, VIVA, UCL, PhD Giles Kendall, 5/10/2009; Internal Examiner, VIVA, ICL, PhD
Shirin Khanjani 18 / 3 / 2010; Examiner, PhD upgrade, ICL, Lynne Sykes, 2/3/2010; Assessment of PhD proposal, ICL, Lynne Sykes,
26/11 / 2008; Co-examiner VIVA, MSc, Caroline Copeland, 9/3/2009; Opponent ( = external examiner) disputation ( = VIVA) in Lund
University, Sweden, Ph D Tina Markus 30 / 5 / 2009
Awards
Young scientist award of 1990 at European Society for Neurochemistry (ESN) and invited to give a Honorary lecture at the ESN
meeting in Leipzig, July 1990
Recipient of The Eric Fernstrm Price (100.000 SEK) in Lund, Sweden, 1996
Recipient of a Fullbright Scholarship for one year (2000-2001) of research at Kennedy Krieger Institute, Johns Hopkins School of
Medicine, Baltimore, USA. Host: prof M Johnston.
Recipient of the Lennander Award and presentation of the yearly Lennander lecture (one researcher is selected every year of all
scientists in Surgical disciplines and infectious diseases in Sweden) at the Swedish Medical Society, Stockholm, Sweden, 2008
Elected member of scientific peer review committees and scientific committees
Reviewer of LUA grant applications in Gteborg, on behalf of the Medical Faculty 1997-present
Reviewer for the National Brain Foundation (Hjrnfonden), 1998-2003
Reviewer for the National Network in Neuroscience (NNN), 1998-1999
Member of the Research Committee (Forskningsnmden ordinarie ledamot) of the Medical Faculty, Gteborg University, Sweden,
1997-2000
Member of the committee for research education (Forskarutbildningskommittn), 1997-2000
Member of the Nominating Committee, Sahlgrenska Academy 2005-2008
Reviewer for Swedish Research Council, 2011 and 2013
Networks in academia
Professor M.V Johnston, Kennedy Krieger Institute, Johns Hopkins School of Medicine, Baltimore, USA johnston@kennedykrieger.org
Professor A.D. Edwards, Kings College London, London, U.K., ad.edwards@kcl.ac.uk
Professor Susan Vannucci, Columbia University, New York, USA sv2020@columbia.edu
Professor Pierre Gressens, Inserm 676, Paris, France & Kings College London, London, UK, pierre.gressens@inserm.fr
Entrepreneurial achievements
External advisor for the neuroprotection drug development at Cerebrovascular Disorders, Hoechst AG, 1987-1995
Member of the international advisory board at Neurophyxia (development of brain protective drugs for newborns) October 2003-2009
Invitations / specific tasks
Invited speaker at 186 international meetings and 12 national scientific meetings 1988-2013.
Previous PhD-students: 30 PhD-students
Peter Andin, 1992, Consultant in Psychiatry; Klas Ostwald, 1994, Assistant Professor; Bo Sultan, 1994, Director of Ob/Gyn in
lvngen, Norway; Mats Blennow, 1995, Head in Neonatology Karolinska Institute, Assistant Professor; Ralph Bgenholm, 1995,
Consultant in Neurology; Elsa Bona, 1997, Consultant in Pediatrics; Eric Gilland, 1997, Consultant in Neurology; Ulla-Britt Wennerholm,
1998, Assistant Professor and Consultant in Obstetrics and Gynecology; M Puka-Sundvall, 2000, Teacher of Natural Sciences; Camilla
Revesj, 2000, Bachelor of Medicine; Karin Svman, 2001, Consultant in Neonatology; Ellen Samuelsson, 2002, Research Midwife; Bo
Jacobsson, 2003, Consultant in Obstetrics and Research fellow; Lena Mrtensson, 2003, Head at Skvde University; Ulrika Hallin, 2004,
Bachelor of Medicine Xiaoyang Wang, 2004, Research fellow and consultant in Pediatrics; Maj Hedtjrn, 2004, Research Fellow;
Katarina Brywe, 2004, Consultant in Obstetrics; Saskia Eklind, 2004, Consultant in Gynecology; Changlian Zhu, 2004, Research fellow
and Head of Neonatology; Anna-Karin Welin, 2005, Consultant in Obstetrics; Malin Gustavsson, 2005, Research assistant; Margareta
Mollberg, 2007, Senior lecturer: Helen Elden, 2008, Senior lecturer; Pernilla Svedin, 2008, Research assistant; Hkan Norn, 2008,
Consultant in Obstetrics and Gynecology, Rose-Marie Holst, 2009, Consultant in Obstetrics and Gynecology; Christina Doverhag, 2010,
Research assistant; Katarina Jrlestedt, 2010, Research assistant; Ylva Carlsson, 2011, Consultant in Obstetrics.
Other Qualification
Funding 3.0 MSEK / year including grants from the Swedish Research Council, EU and ALF; UK MRC award 2008-2011 1 M UK
pounds, Leducq Foundation 1 MSD / year 2011-2016, Wellcome Trust 2010-2015 1,1 M UK pounds, Sparks 150k GBP 2013-2015.
Research publications: 256 original articles, 2 manuscripts and 57 reviews or book chapters. H-index: 62, average citation/article: 31

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Abstracts for The 46th International Congress on Pathophysiology of Pregnancy