Quantitative assessment of new cell proliferation in the dentate gyrus and learning after isoflurane or propofol anesthesia in young and aged rats

Erasso, Diana M.; Chaparro, Rafael E; Rio, Carolina E. Quiroga del; Karlnoski, Rachel; Camporesi, Enrico M.; Saporta, Samuel

doi:10.1016/j.brainres.2011.11.025

Cited by 28 publications

(21 citation statements)

References 40 publications

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“…It is difficult to separate the effects of surgery, anesthesia, and comorbidity in clinical studies. However, multiple independent investigations conducted in rodent models using different anesthetics and varying exposure paradigms in the absence of surgery indicate that early developmental exposure to general anesthetic agents results in lasting impairment on behavioral measures of neurocognitive function, predominantly in the domain of learning and memory [4–12]. While 2 recent clinical studies give some reassurance that short, single exposures in healthy children may not have dramatic consequences [13,14], clear evidence of lasting cognitive deficits was detected recently in a carefully conducted study of a somewhat longer clinically relevant anesthetic exposure in nonhuman primates [15].…”

Section: Introductionmentioning

confidence: 99%

Early postnatal exposure to isoflurane causes cognitive deficits and disrupts development of newborn hippocampal neurons via activation of the mTOR pathway

et al. 2017

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Clinical and preclinical studies indicate that early postnatal exposure to anesthetics can lead to lasting deficits in learning and other cognitive processes. The mechanism underlying this phenomenon has not been clarified and there is no treatment currently available. Recent evidence suggests that anesthetics might cause persistent deficits in cognitive function by disrupting key events in brain development. The hippocampus, a brain region that is critical for learning and memory, contains a large number of neurons that develop in the early postnatal period, which are thus vulnerable to perturbation by anesthetic exposure. Using an in vivo mouse model we demonstrate abnormal development of dendrite arbors and dendritic spines in newly generated dentate gyrus granule cell neurons of the hippocampus after a clinically relevant isoflurane anesthesia exposure conducted at an early postnatal age. Furthermore, we find that isoflurane causes a sustained increase in activity in the mechanistic target of rapamycin pathway, and that inhibition of this pathway with rapamycin not only reverses the observed changes in neuronal development, but also substantially improves performance on behavioral tasks of spatial learning and memory that are impaired by isoflurane exposure. We conclude that isoflurane disrupts the development of hippocampal neurons generated in the early postnatal period by activating a well-defined neurodevelopmental disease pathway and that this phenotype can be reversed by pharmacologic inhibition.

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Section: Introductionmentioning

confidence: 99%

Early postnatal exposure to isoflurane causes cognitive deficits and disrupts development of newborn hippocampal neurons via activation of the mTOR pathway

et al. 2017

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“…Deficits were found with exposure at PND 14, a later age than previously studies, suggesting the possibility of a distinct mechanism of toxicity. Reductions in neurogenesis have also been observed following early exposure to other anesthetic agents, including sevoflurane and propofol 48, 49 . Experimentation in cell culture models using neuronal precursors also suggests that isoflurane and sevoflurane exposure can inhibit neurogenesis 45, 50 .…”

Section: Effects Of Anesthetics On Neurogenesismentioning

confidence: 98%

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Wagner

Ryu

Smith

et al. 2014

Journal of Neurosurgical Anesthesiology

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The results of several retrospective clinical studies suggest that exposure to anesthetic agents early in life is correlated with subsequent learning and behavioral disorders. While ongoing prospective clinical trials may help to clarify this association, they remain confounded by numerous factors. Thus, some of the most compelling data supporting the hypothesis that a relatively short anesthetic exposure can lead to a long-lasting change in brain function are derived from animal models. The mechanism by which such changes could occur remains incompletely understood. Early studies identified anesthetic-induced neuronal apoptosis as a possible mechanism of injury, and more recent work suggests that anesthetics may interfere with several critical processes in brain development. The function of the mature brain requires the presence of circuits, established during development, that perform the computations underlying learning and cognition. In this review we examine the mechanisms by which anesthetics could disrupt brain circuit formation, including effects on neuronal survival and neurogenesis, neurite growth and guidance, formation of synapses, and function of supporting cells. There is evidence that anesthetics can disrupt aspects of all of these processes, and further research is required to elucidate which are most relevant to pediatric anesthetic neurotoxicity.

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“…For hematoxylin staining, the sections were stained with Mayer's hematoxylin (MUTO, Tokyo, Japan) according to the manufacturer's instructions. The sections were cover slipped with mounting medium (Permount; Fisher Scientific, Pittsburgh, PA, USA) (Erasso et al, 2012) and observed under a bright-field microscope (Model BX54, Olympus Optical, Tokyo, Japan). Bright field images were obtained using the Picture Frame Application 2.3 software (Olympus Optical).…”

Section: Bromodeoxyuridine Treatment and Immunohistochemistrymentioning

confidence: 99%

Effect of whole-body exposure to the 848.5 MHz code division multiple access (CDMA) electromagnetic field on adult neurogenesis in the young, healthy rat brain

Kim

Lee

et al. 2015

International Journal of Radiation Biology

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Quantitative assessment of new cell proliferation in the dentate gyrus and learning after isoflurane or propofol anesthesia in young and aged rats

Cited by 28 publications

References 40 publications

Early postnatal exposure to isoflurane causes cognitive deficits and disrupts development of newborn hippocampal neurons via activation of the mTOR pathway

Early postnatal exposure to isoflurane causes cognitive deficits and disrupts development of newborn hippocampal neurons via activation of the mTOR pathway

Review

Effect of whole-body exposure to the 848.5 MHz code division multiple access (CDMA) electromagnetic field on adult neurogenesis in the young, healthy rat brain

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