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Isoflurane affects the cytoskeleton but not survival, proliferation, or synaptogenic properties of rat astrocytes in vitro

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TLDR
Isoflurane decreased expression of microtubule and intermediate filament proteins in astrocytes in vitro, but did not affect their viability, proliferation, motility, and ability to support synapses.
Abstract
Background More than half of the cells in the brain are glia and yet the impact of general anaesthetics on these cells is largely unexamined. We hypothesized that astroglia, which are strongly implicated in neuronal well-being and synapse formation and function, are vulnerable to adverse effects of isoflurane. Methods Cultured rat astrocytes were treated with 1.4% isoflurane in air or air alone for 4 h. Viability, proliferation, and cytoskeleton were assessed by colorimetric assay, immunocytochemistry, or a migration assay at the end of treatment or 2 days later. Also, primary rat cortical neurones were treated for 4 days with conditioned medium from control [astrocyte-conditioned media (ACM)], or isoflurane-exposed astrocytes (Iso-ACM) and synaptic puncta were assessed by synapsin 1 and PSD-95 immunostaining. Results By several measures, isoflurane did not kill astrocytes. Nor, based on incorporation of a thymidine analogue, did it inhibit proliferation. Isoflurane had no effect on F-actin but reduced expression of α-tubulin and glial fibrillary acidic protein both during exposure ( P P P Conclusions Isoflurane decreased expression of microtubule and intermediate filament proteins in astrocytes in vitro , but did not affect their viability, proliferation, motility, and ability to support synapses.

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Perioperative Neurocognitive Disorder: State of the Preclinical Science.

TL;DR: The authors' goal is to improve the quality and consistency of postoperative cognitive dysfunction and perioperative neurocognitive disorder research by promoting optimal study design, enhanced transparency, and "best practices" in experimental design and reporting to increase the likelihood of corroborating results.
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Neurodevelopmental Implications of the General Anesthesia in Neonate and Infants

TL;DR: Animal and clinical studies indicate that exposure to general anesthetics may affect CNS development, resulting in long-lasting cognitive and behavioral deficiencies, such as learning and memory deficits, as well as abnormalities in social memory and social activity.
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Anesthesia, Brain Changes, and Behavior: Insights from Neural Systems Biology.

TL;DR: The available preclinical and clinical data on the developing and aging brain, and in known vulnerable populations are critically evaluated to provide insights into potential changes that may affect the general population of patients in a more, subtle manner.
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Anesthetic neurotoxicity in the newborn and infant.

TL;DR: Whether anesthesia-associated neurotoxicity affects the developing human brain and whether this leads to clinically measurable deficits remains unclear.
References
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Journal ArticleDOI

Rho GTPases in cell biology.

TL;DR: Rho GTPases are molecular switches that control a wide variety of signal transduction pathways in all eukaryotic cells and their ability to influence cell polarity, microtubule dynamics, membrane transport pathways and transcription factor activity is probably just as significant.
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Early Exposure to Common Anesthetic Agents Causes Widespread Neurodegeneration in the Developing Rat Brain and Persistent Learning Deficits

TL;DR: A combination of drugs commonly used in pediatric anesthesia in doses sufficient to maintain a surgical plane of anesthesia is administered to 7-d-old infant rats, and it is observed that this causes widespread apoptotic neurodegeneration in the developing brain, deficits in hippocampal synaptic function, and persistent memory/learning impairments.
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Control of synapse number by glia.

TL;DR: It is shown that few synapses form in the absence of glial cells and that the fewsynapses that do form are functionally immature, and that CNS synapse number can be profoundly regulated by nonneuronal signals.
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The Mystery and Magic of Glia: A Perspective on Their Roles in Health and Disease

TL;DR: It is argued that until the roles of nonneuronal cells are more fully understood and considered, neurobiology as a whole will progress only slowly.
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Three-Dimensional Relationships between Hippocampal Synapses and Astrocytes

TL;DR: In this paper, the authors investigated structural relationships between hippocampal astrocytes and synapses in stratum radiatum of hippocampal area CA1 in the mature rat in vivo and in slices.
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