title: Toxicity to sensory neurons and Schwann cells in experimental linezolid-induced peripheral neuropathy.
abstract: OBJECTIVE
  Peripheral neuropathy is a common side effect of prolonged treatment with linezolid. This study aimed to explore injurious effects of linezolid on cells of the peripheral nervous system and to establish in vivo and in vitro models of linezolid-induced peripheral neuropathy.
  
  
  METHODS
  C57BL/6 mice were treated with linezolid or vehicle over a total period of 4 weeks. Animals were monitored by weight, nerve conduction studies and behavioural tests. Neuropathic changes were assessed by morphometry on sciatic nerves and epidermal nerve fibre density in skin sections. Rodent sensory neuron and Schwann cell cultures were exposed to linezolid in vitro and assessed for mitochondrial dysfunction.
  
  
  RESULTS
  Prolonged treatment with linezolid induced a mild, predominantly small sensory fibre neuropathy in vivo. Exposure of Schwann cells and sensory neurons to linezolid in vitro caused mitochondrial dysfunction primarily in neurons (and less prominently in Schwann cells). Sensory axonopathy could be partially prevented by co-administration of the Na(+)/Ca(2+) exchanger blocker KB-R7943.
  
  
  CONCLUSIONS
  Clinical and pathological features of linezolid-induced peripheral neuropathy can be replicated in in vivo and in vitro models. Mitochondrial dysfunction may contribute to the axonal damage to sensory neurons that occurs after linezolid exposure.
authors.affiliation: Department of Neurology, University Hospital of Cologne, Cologne, Germany Centre for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
authors.forename: Ilja
authors.initials: I
authors.lastname: Bobylev
authors.affiliation: Department of Neurology, University Hospital of Cologne, Cologne, Germany Centre for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
authors.forename: Helina
authors.initials: H
authors.lastname: Maru
authors.affiliation: Department of Neurology, University Hospital of Cologne, Cologne, Germany Centre for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
authors.forename: Abhijeet R
authors.initials: AR
authors.lastname: Joshi
authors.affiliation: Department of Neurology, University Hospital of Cologne, Cologne, Germany Centre for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany helmar.lehmann@uk-koeln.de.
authors.forename: Helmar C
authors.initials: HC
authors.lastname: Lehmann
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D000069349:Linezolid / Q000009:adverse effects*; D008297:Male; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology; D012583:Schwann Cells / Q000187:drug effects* / Q000502:physiology*; D012584:Sciatic Nerve / Q000473:pathology; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000502:physiology*; D012867:Skin / Q000473:pathology
chemical_list: D000900:Anti-Bacterial Agents; D000069349:Linezolid