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Millions of children are treated every year with anesthetics and sedatives to facilitate surgical procedures and to provide sedation in emergency and intensive care. In addition to rendering patients insensible to painful stimuli, these compounds have numerous other effects, some of them protective, while others may be deleterious. Accordingly, our laboratory examines the effects of anesthetics and sedatives on the developing brain.
Thousands of infants require complex surgical procedures early in life, such as neurosurgery, surgery for inherent malformations or repair of congenital heart disease, which may predispose them to hemodynamic instability and periods of inadequate supply of oxygen and blood flow (hypoxia-ischemia) to their immature brains, potentially resulting in brain damage and long-term developmental abnormalities. Our research efforts are directed toward improving the detection of hypoxic and hypoxic-ischemic episodes using noninvasive techniques, to identify the mechanisms of hypoxic and hypoxic-ischemic brain injury, to characterize neurological injury and subsequent neurocognitive outcome, as well as to develop treatment strategies, with a special focus on anesthetics.
Mounting evidence from animal studies has implicated all commonly used anesthetics and sedatives to induce widespread neuronal cell death, resulting in long-term neurological abnormalities under certain conditions. These findings have raised serious concerns regarding the safe use of these medications in young children. Our research sets out to clarify the underlying mechanisms of anesthesia-induced neurotoxicity and the selectivity of the phenomenon, which will be critical for assessing its human relevance, and if necessary, for discovering mitigating therapies. Moreover, our preclinical research aims to identify biomarkers of anesthesia-induced developmental neuroapoptosis. Our clinical research efforts are directed toward examining the phenomenon’s long-term brain morphological effects using non-invasive imaging technology. Moreover, we are participating in a multicenter trial, the PANDA study, which investigates the long-term neurobehavioral effects of surgery with anesthesia early in life.
Our laboratory offers research opportunities at the undergraduate, graduate and postgraduate levels, including training for residents and fellows as part of the Pediatric Anesthesia Fellowship in the Department of Anesthesia at Cincinnati Children’s Hospital Medical Center, as well as the Neuroscience Graduate Program at the University of Cincinnati.
Loepke AW, Soriano SG. Impact of Pediatric Surgery and Anesthesia on Brain Development. Pediatric Anesthesia. 5th Edition. Edited by Gregory GA & Andropoulos DB. Wiley-Blackwell Publishing, Oxford, UK, 2011. In press.
Wise-Faberowski L, Loepke AW. Anesthesia During Surgical Repair for Congenital Heart Disease and the Developing Brain: Neurotoxic or Neuroprotective?Paediatr Anaesth. 2011. In press.
Boat A, Sadhasivam S, Loepke AW, Kurth CD. Outcome for the extremely premature neonate: how far do we push the edge? Paediatr Anaesth. 2011.
Murphy BL, Pun RYK, Yin H, Faulkner CR, Loepke AW, Danzer SC. Heterogeneous Integration of Adult-Generated Granule Cells Into the Epileptic Brain. J Neurosci. 31(1):105-17. 2011.
Istaphanous GK, Howard J, Nan X, Hughes EA, McCann JC, McAuliffe JJ, Danzer SC, Loepke AW. Comparison of the Neuroapoptotic Properties of Equipotent Anesthetic Concentrations of Desflurane, Isoflurane, or Sevoflurane in Neonatal Mice. Anesthesiology 114(3): 578-87. 2011.
Istaphanous GK, Loepke AW. Pediatric Pulmonary Hypertension. Clinical Pediatric Anesthesia: A Case-Based Handbook, 1st Edition. Edited by Goldschneider K, Davidson A, Wittkugel E, and Skinner A. Oxford University Press, Oxford, UK, 2011. In press.
Lin EP, Loepke AW. Cardiac Catheterization. Clinical Pediatric Anesthesia: A Case-Based Handbook, 1st Edition. Edited by Goldschneider K, Davidson A, Wittkugel E, and Skinner A. Oxford University Press, Oxford, UK, 2011. In press.
Istaphanous GK, Ward CG, Loepke AW. The Impact of the Perioperative Period on Neurocognitive Development, with a Focus on Pharmacological Concerns. Best Pract Res Clin Anaesthesiol. 24(3): 433-449. 2010.
Liang G, Ward CG, Peng J, Zhao Y, Huang B, Wei H. Isoflurane causes greater neurodegeneration than an equivalent exposure of sevoflurane in the developing brain of neonatal mice. Anesthesiology. 112(6):1325-34. 2010.
Spaeth JP, Loepke AW. Anesthesia for Left-Sided Obstructive Lesions. Anesthesia for Congenital Heart Disease. 2nd Edition. Edited by Andropoulos DB, Stayer SA, Russell IA. Wiley-Blackwell, 398-418. 2010.
Loepke AW. Developmental neurotoxicity of sedatives and anesthetics: a concern for neonatal and pediatric critical care medicine? Pediatr Crit Care Med. 11(2): 217-226. 2010.
Stratmann G, Sall JW, May LDV, Loepke AW, Lee MT. Beyond Anesthetic Properties: Effects of Inhalational on Brain Cell Death, Neurogenesis and Long-Term Neurocognitive Function. Anesth Analg. 110(2): 431-437. 2010.
Danzer SC, He X, Loepke AW, McNamara JO. Structural plasticity of dentate granule cell mossy fibers during the development of limbic epilepsy. Hippocampus. 20(1): 113-124. 2010.
McAuliffe JJ, Loepke AW, Miles L, Joseph B, Hughes E, Vorhees CV. Desflurane, isoflurane, and sevoflurane provide limited neuroprotection against neonatal hypoxia-ischemia in a delayed-preconditioning paradigm. Anesthesiology. 111(3): 533-46. 2009.
Istaphanous GK, Loepke AW. General anesthetics and the developing brain. Current Opinion in Anesthesiology. 22(3): 368-373. 2009.
Kurth CD, McCann JC, Wu J, Miles L, Loepke AW. Cerebral oxygen saturation-time threshold for hypoxic-ischemic injury in piglets. Anesth Analg. 108(4): 1268-77. 2009.
Loepke AW, Istaphanous GK, McAuliffe JJ, Miles L, Hughes EA, McCann JC, Harlow KE, Kurth CD, Williams MT, Vorhees CV, Danzer SC. The effects of neonatal isoflurane exposure in mice on brain cell viability, adult behavior, learning, and memory. Anesth Analg. 108(1): 90-104. 2009.
Loepke AW, Soriano SG. An assessment of the effects of general anesthetics on developing brain structure and neurocognitive function. Anesth Analg. 106: 1681-1707. 2008.
Loepke AW, McGowan FX, Soriano SG. CON: The toxic effects of anesthetics in the developing brain: the clinical perspective. Anesth Analg. 106: 1664-9. 2008.
Loepke AW, McCann JC, Kurth CD, McAuliffe JJ. The physiologic effects of isoflurane anesthesia in neonatal mice. Anesth Analg. 102: 75-80. 2006.
Loepke AW, Golden, JA, McCann JC, Kurth CD. Injury pattern of the neonatal brain after low-flow cardiopulmonary bypass in a piglet model. Anesth Analg. 101: 340-8. 2005.
Ditsworth D, Priestley MA, Loepke AW, Ramamoorthy C, McCann JC, Staple L, Kurth CD. Apoptotic Neuronal Death Following Deep Hypothermic Circulatory Arrest in Piglets. Anesthesiology. 98: 1119-27. 2003.
Loepke AW, Priestley MA, Schultz SE, McCann JC, Kurth CD. Desflurane Improves Outcome After Low-Flow Cardiopulmonary Bypass in Newborn Pigs. Anesthesiology. 97: 1521-7. 2002.
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