Anesthetic neuropharmacology and physiology
We study acute and long-term effects of anesthesia and surgery on vital regulatory control of consciousness, cognition and respiration.
Our research group focuses on translational studies of the most common acute and long-term adverse effects of anesthesia and surgery within vital regulatory control of ventilation, consciousness and cognition. Primarily caused by trauma-induced inflammation and residual effects of anesthetic drugs, impaired ventilatory control and cognitive function are key factors behind morbidity and mortality in both young and adult surgical patients.
Our project focus is on master regulatory pathways within the cholinergic and innate immune systems that ultimately cooperate in regulation of vital brain functions after surgical trauma. Over two decades, our group has developed a broad translational research platform including human clinical and experimental technologies combined with advanced imaging and large-scale national outcome investigations as well as animal, cellular and molecular in vitro, in vivo/ex vivo techniques.
This field of research targets the most common long-term adverse effects of surgery and anesthesia within a large segment of postoperative patients with considerable relevance for clinical practice and health care systems. Our research will gain comprehensive insights into basic principles for recovery of brain function and improved postoperative care after surgical trauma and critical illness, and will provide novel therapeutic strategies of relevance for improved patient safety and reduced morbidity.
Cognitive decline and neuroinflammation after anesthesia and surgery
In this translational project we uncover pivotal mechanisms underlying postoperative impairment of brain functions related to cognitive performance, such as long-term reductions in memory, learning and attention capacity. In this context, we target master regulatory pathways within cholinergic signaling, innate immunity and inflammation involved in central nervous system complications after anesthesia and surgical trauma.
We translate findings in relevant animal, cellular and molecular trauma-models into surgical patient care by studying the impact of surgery and anesthesia on cognitive functions and immune activation within the central nervous system of surgical patients. Here we apply arrays of advanced neuroimaging techniques combined with longitudinal biomarker analysis and serial cognitive testing in both observational and interventional clinical trials.
Effects of surgery and anesthesia on the central nervous system
The impact of exposure to surgery or intensive care in early childhood or later adult life for long-term cognitive outcome and risk for permanent dementia.
We furthermore explore the association between exposure for anesthesia and surgery in early childhood and later cognitive performance using combined information from the Swedish National Inpatient Register, the Swedish Twin registry, the school system and the military conscription registry. In a separate analysis we explore the role of hospitalization, surgery and critical illness among adults for long-term cognitive outcome after intensive care and surgery, and the risk for permanent cognitive decline and dementia.
Respiratory control - the human carotid body as oxygen and inflammatory sensor
This part uncovers fundamental principles behind human defense mechanisms within hypoxic respiratory control and inflammatory sensoring, focusing on human carotid body oxygen and inflammatory sensing pathways of relevance for anesthesia and surgery. Using animal, cellular and molecular models of specialized oxygen sensing and immune cells within the carotid bodies, we map the human carotid body oxygen and inflammatory genotype and phenotype, with focus on key sensing genes and molecules, cholinergic transmission and ATP. We also explore the nature of pharyngeal and respiratory integration of relevance for respiratory control and airway integrity in young and aged patients after exposure to anesthesia and surgery.
- Swedish Research Council (VR)
- "Kunskapsluckor inom vården" - Swedish Research Council
- Stockholm County Council (ALF grant)
- European Society of Anaesthesiology
- Karolinska Institutet
- Stockholms frimurarlogernas hyllningsfonder
- Torsten Söderberg's foundation (page in Swedish)
Pharyngeal function and breathing pattern during partial neuromuscular block in the elderly: effects on airway protection.
Cedborg AI, Sundman E, Bodén K, Hedström HW, Kuylenstierna R, Ekberg O, et al
Anesthesiology 2014 Feb;120(2):312-25
The human carotid body transcriptome with focus on oxygen sensing and inflammation--a comparative analysis.
Mkrtchian S, Kåhlin J, Ebberyd A, Gonzalez C, Sanchez D, Balbir A, et al
J. Physiol. (Lond.) 2012 Aug;590(16):3807-19
Malignant disease within 5 years after surgery in relation to duration of sevoflurane anesthesia and time with bispectral index under 45.
Lindholm ML, Granath F, Eriksson LI, Sandin R
Anesth. Analg. 2011 Oct;113(4):778-83
Perioperative cognitive decline in the aging population.
Terrando N, Brzezinski M, Degos V, Eriksson LI, Kramer JH, Leung JM, et al
Mayo Clin. Proc. 2011 Sep;86(9):885-93
Resolving postoperative neuroinflammation and cognitive decline.
Terrando N, Eriksson LI, Ryu JK, Yang T, Monaco C, Feldmann M, et al
Ann. Neurol. 2011 Dec;70(6):986-995
The human carotid body: expression of oxygen sensing and signaling genes of relevance for anesthesia.
Fagerlund MJ, Kåhlin J, Ebberyd A, Schulte G, Mkrtchian S, Eriksson LI
Anesthesiology 2010 Dec;113(6):1270-9
Pharmacological characteristics of the inhibition of nondepolarizing neuromuscular blocking agents at human adult muscle nicotinic acetylcholine receptor.
Jonsson Fagerlund M, Dabrowski M, Eriksson LI
Anesthesiology 2009 Jun;110(6):1244-52
Co-ordination of spontaneous swallowing with respiratory airflow and diaphragmatic and abdominal muscle activity in healthy adult humans.
Hårdemark Cedborg AI, Sundman E, Bodén K, Hedström HW, Kuylenstierna R, Ekberg O, et al
Exp. Physiol. 2009 Apr;94(4):459-68
Sevoflurane anesthesia alters exploratory and anxiety-like behavior in mice lacking the beta2 nicotinic acetylcholine receptor subunit.
Wiklund A, Granon S, Cloëz-Tayarani I, Faure P, le Sourd AM, Sundman E, et al
Anesthesiology 2008 Nov;109(5):790-8