title: Isoflurane affects the cytoskeleton but not survival, proliferation, or synaptogenic properties of rat astrocytes in vitro.
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<0.05 and P<0.001, respectively) and 2 days later (P<0.01), but did not impair astrocyte motility. ACM increased formation of PSD-95 but not synapsin 1 positive puncta in neuronal cultures, and Iso-ACM was equally effective.
  
  
  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.
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. dculley@zeus.bwh.harvard.edu
authors.forename: D J
authors.initials: DJ
authors.lastname: Culley
authors.forename: E K
authors.initials: EK
authors.lastname: Cotran
authors.forename: E
authors.initials: E
authors.lastname: Karlsson
authors.forename: A
authors.initials: A
authors.lastname: Palanisamy
authors.forename: J D
authors.initials: JD
authors.lastname: Boyd
authors.forename: Z
authors.initials: Z
authors.lastname: Xie
authors.forename: G
authors.initials: G
authors.lastname: Crosby
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000648:ultrastructure; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D007530:Isoflurane / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects*
chemical_list: D018685:Anesthetics, Inhalation; D017077:Culture Media, Conditioned; D003598:Cytoskeletal Proteins; D007530:Isoflurane
keywords: astrocytes; isoflurane