General anesthetics induce apoptotic neurodegeneration in the neonatal rat spinal cord.
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.
Sanders
Robert D
RD
Department of Anaesthetics, Pain Medicine and Intensive Care, Imperial College London, Chelsea & Westerminster Hospital, London, UK.
Xu
Jing
J
Shu
Yi
Y
Fidalgo
Antonio
A
Ma
Daqing
D
Maze
Mervyn
M
D018681:Anesthetics, General / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D004789:Enzyme Activation; D007530:Isoflurane / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D009609:Nitrous Oxide / Q000633:toxicity*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development / Q000473:pathology
D018681:Anesthetics, General; D007530:Isoflurane; C505410:Casp3 protein, rat; D053148:Caspase 3; D009609:Nitrous Oxide