Overview
Our laboratory examines the effects of anesthetics on the developing brain. For over 160 years inhalational and intravenous anesthetics have been used to provide general anesthesia, one of the greatest inventions of all time, for millions of patients. Although the exact molecular mechanisms by which these compounds render patients insensible to painful procedures are not entirely understood, there exists an abundant selection of potential targets. Anesthetics have been shown to interact with a wide variety of ion channels, such as sodium, calcium, and potassium channels, and with numerous neuronal receptors, such as γ-aminobutyrate, glycine, glutamate, nicotine, and serotonin receptors. It is therefore not surprising that several anesthetics, in addition to providing unconsciousness, also have many other effects, which could be either potentially harmful or could be beneficial and employed for therapeutic use.
Accordingly, our group investigates the ability of inhalational anesthetics to provide beneficial effects during periods of inadequate blood supply and oxygenation to the brain, such as in hypoxic-ischemic brain injury related to congenital heart disease. Despite the improvement in survival after congenital heart surgery, up to 40% of survivors still suffer from neurological abnormalities, such as developmental delay, motor dysfunction, seizures, and cerebral palsy. Our work aims to identify the mechanism of this injury and to develop therapies for prevention, with special focus on the use of inhalational anesthetics. Along those lines, our experimental findings of protective effects by inhalational anesthetics in this setting have contributed to a shift in the anesthetic management during pediatric open-heart surgery towards increased use of inhalational anesthetics.
Recent experimental data in developing brain models have demonstrated anesthesia-induced neuronal degeneration. This phenomenon has raised significant concerns regarding the safety of anesthesia in human neonates and infants. Our laboratory aims to clarify the mechanism and selectivity of anesthesia-induced neurotoxicity, which will be critical for assessing relevance to human health, and if necessary, for discovering mitigating therapies.
To achieve our objectives we utilize model systems of the developing brain, using immunohistochemistry, confocal microscopy, behavioral testing paradigms, organotypic slice cultures, and transgenic models. Our research has received several awards and has been recognized by a variety of regional, national, and international organizations, including the Midwest Anesthesia Resident Conference, the Society for Pediatric Anesthesia, the International Anesthesia Research Society, the Foundation for Anesthesia Education and Research, and the American Society of Anesthesiologists. We closely collaborate with other neurobiology groups, both nationally and internationally. Our laboratory offers research training at the undergraduate, graduate, and postgraduate level, including research opportunities for residents and fellows as part of the Pediatric Anesthesia Fellowship in the Department of Anesthesia at Cincinnati Children’s Hospital Medical Center. Our laboratory also participates in the Neuroscience Graduate Program at the University of Cincinnati.
Publications
Loepke AW, Istaphanous GK, McAuliffe JJ, Miles L, Hughes EA, McCann JC, Harlow KE, Kurth CD, Williams MT, Vorhees CV, Danzer SC (in press) The Effects of Neonatal Isoflurane Exposure in Mice on Brain Cell Viability, Adult Behavior, Learning, and Memory. Anesth Analg
Loepke AW, Soriano SG (2008) An Assessment of the Effects Of General Anesthetics on Developing Brain Structure and Neurocognitive Function. Anesth Analg 106: 1681-1707
Loepke AW, McGowan FX, Soriano SG (2008) The Toxic Effects of Anesthetics in The Developing Brain: The Clinical Perspective. Anesth Analg 106: 1664-9
Nelson LA, McCann JC, Loepke AW, Wu J, Dor BB, Kurth CD (2006) Development and Validation of a Multiwavelength Spatial Domain Near-Infrared Oximeter to Detect Cerebral Hypoxia-Ischemia. J Biomed Opt 11(6): 064022
Loepke AW, McCann JC, Kurth CD, McAuliffe JJ (2006) Physiologic Effects of Isoflurane Anesthesia in Neonatal Mice. Anesth Analg 102: 75-80
Loepke AW, Golden, JA, McCann JC, Kurth CD (2005) Injury Pattern of the Neonatal Brain After Low-Flow Cardiopulmonary Bypass in a Piglet Model. Anesth Analg 101: 340-8
Soriano SG, Loepke AW (2005) Let’s Not Throw the Baby Out With the Bath Water - Potential Neurotoxicity of Anesthetic Drugs in Infants and Children. J Neurosurg Anesthesiol 17: 207-9
Loepke AW, Spaeth JP (2004) Glucose And Heart Surgery: Neonates Are Not Just Small Adults. Anesthesiology 100: 1339-41
Galinkin JL, Kurth CD, Shi H, Priestley MA, Loepke AW, Adamson PC (2004) The Plasma Pharmacokinetics and Cerebral Spinal Fluid Penetration of Intravenous Topiramate in Newborn Pigs. Biopharmaceutics & Drug Disposition 25: 265-71
Ditsworth D, Priestley MA, Loepke AW, Ramamoorthy C, McCann JC, Staple L, Kurth CD (2003) Apoptotic Neuronal Death Following Deep Hypothermic Circulatory Arrest in Piglets. Anesthesiology 98: 1119-27
Loepke AW, Priestley MA, Schultz SE, McCann JC, Kurth CD (2002) Desflurane Improves Outcome After Low-Flow Cardiopulmonary Bypass in Newborn Pigs. Anesthesiology 97: 1521-7
Contact
Andreas W. Loepke, MD, PhD
Associate Professor,
Clinical Anesthesia and Pediatrics
Department of Anesthesia
Cincinnati Children’s Hospital Medical Center
3333 Burnet Ave.
Cincinnati, OH 45229
Telephone: 513-636-4408
Fax: 513-636-7337
Email: Andreas.Loepke@cchmc.org
