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PEDIATRIC ANESTHESIOLOGY

General Anesthetics Induce Apoptotic Neurodegeneration in the Neonatal Rat Spinal Cord

Robert D. Sanders, BSc, MBBS^*, Jing Xu, MD, Yi Shu, BSc^*, Antonio Fidalgo, MSc^*, Daqing Ma, MD, PhD^*, and Mervyn Maze, MB ChB, FRCA, FRCP, FMedSci^*

From the *Departments of Anaesthetics, Pain Medicine and Intensive Care, Imperial College London, Chelsea & Westerminster Hospital, London; and Department of Anesthesiology, Gongli Hospital, Pudong, Shanghai, China.

Address correspondence and reprint requests to Dr. Daqing Ma, Department of Anaesthetics, Pain Medicine and Intensive Care, Imperial College London SW10 9NH. Address e-mail to d.ma{at}imperial.ac.uk.

Abstract

BACKGROUND: Exposure to anesthetics triggers apoptotic neurodegeneration in the neonatal rat brain; whether neuronal apoptosis also occurs in the spinal cord, a crucial target for analgesic and anesthetic drugs, is unknown.

METHODS: We exposed 7-day-old rats were exposed to air or 75% nitrous oxide + 0.75% isoflurane in oxygen for 6 h (n = 19 per group). Caspase-3 immunoreactivity was evaluated in the lumbar spinal cord at the end of the gas exposure (n = 3 per group). Developmental nociceptive responses were tested using tail flick latencies on postnatal days 8, 15, and 30 (n = 3 per group). Motor responses were evaluated using the rotarod on postnatal day 30 (n = 7 per group).

RESULTS: Isoflurane plus nitrous oxide increased the numbers of caspase-3 positive neurons in the spinal cord (P < 0.01). Despite a preponderance of the injury in the ventral horn of the spinal cord, motor impairment did not occur (P > 0.05). No functional effect on nociception was observed at the three developmental stages tested (P > 0.05).

CONCLUSIONS: Anesthesia induces apoptosis in the neonatal rat spinal cord; however, the functional consequences of this injury, if any, remain obscure. Neither motor nor nociceptive responses were affected by anesthetic treatment. Nonetheless, further investigation is required as regional anesthetic techniques may also trigger neuroapoptosis in the spinal cord with unknown potency.

This article has been cited by other articles:

				R. D. Sanders, D. Ma, P. Brooks, and M. Maze Balancing paediatric anaesthesia: preclinical insights into analgesia, hypnosis, neuroprotection, and neurotoxicity Br. J. Anaesth., November 1, 2008; 101(5): 597 - 609. [Abstract] [Full Text] [PDF]

				F. X. McGowan Jr and P. J. Davis Anesthetic-Related Neurotoxicity in the Developing Infant: Of Mice, Rats, Monkeys and, Possibly, Humans Anesth. Analg., June 1, 2008; 106(6): 1599 - 1602. [Full Text] [PDF]

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999