Isoflurane anesthesia induced persistent, progressive memory impairment, caused a loss of neural stem cells, and reduced neurogenesis in young, but not adult, rodents.
Isoflurane and related anesthetics are widely used to anesthetize children, ranging from premature babies to adolescents. Concerns have been raised about the safety of these anesthetics in pediatric patients, particularly regarding possible negative effects on cognition. The purpose of this study was to investigate the effects of repeated isoflurane exposure of juvenile and mature animals on cognition and neurogenesis. Postnatal day 14 (P14) rats and mice, as well as adult (P60) rats, were anesthetized with isoflurane for 35 mins daily for four successive days. Object recognition, place learning and reversal learning as well as cell death and cytogenesis were evaluated. Object recognition and reversal learning were significantly impaired in isoflurane-treated young rats and mice, whereas adult animals were unaffected, and these deficits became more pronounced as the animals grew older. The memory deficit was paralleled by a decrease in the hippocampal stem cell pool and persistently reduced neurogenesis, subsequently causing a reduction in the number of dentate gyrus granule cell neurons in isoflurane-treated rats. There were no signs of increased cell death of progenitors or neurons in the hippocampus. These findings show a previously unknown mechanism of neurotoxicity, causing cognitive deficits in a clearly age-dependent manner.
Zhu
Changlian
C
Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. changlian.zhu@neuro.gu.se
Gao
Jianfeng
J
Karlsson
Niklas
N
Li
Qian
Q
Zhang
Yu
Y
Huang
Zhiheng
Z
Li
Hongfu
H
Kuhn
H Georg
HG
Blomgren
Klas
K
D000293:Adolescent; D000328:Adult; D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007530:Isoflurane / Q000494:pharmacology* / Q000633:toxicity; D007858:Learning / Q000187:drug effects; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009483:Neuropsychological Tests; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000187:drug effects* / Q000473:pathology; D016704:Synapsins / Q000378:metabolism
D018685:Anesthetics, Inhalation; D016704:Synapsins; D007530:Isoflurane