title: Methylprednisolone treatment does not influence axonal regeneration or degeneration following optic nerve injury in the adult rat.
abstract: BACKGROUND
  Methylprednisolone (MP) is often used to treat optic nerve injury. However, its effects in experimental crush injury have not been extensively evaluated.
  
  
  METHODS
  Adult Sprague-Dawley rats were subjected to a standardized optic nerve crush injury. Animals were treated either with 30 mg/kg MP intravenous bolus followed by subcutaneous injections every 6 hours for 48 hours, or with a drug vehicle alone.
  
  
  RESULTS
  The injury resulted in a partial loss of neuronal nuclei-labeled retinal neurons and a corresponding degeneration of axons distal to the injury. EDI-labeled macrophages accumulated at the site of lesion, phagocyting FJ-labeled axonal debris. Regenerative fibers expressing growth associated protein-43 were seen proximal to the lesion, but did not traverse the glial scar. Analysis of optic nerve function using visual evoked potentials showed typical signals in intact animals, which were abolished after injury in MP-treated and untreated animals.
  
  
  CONCLUSIONS
  We did not detect any effects of MP on retinal cell survival, macrophage activity at the site of injury, axonal degeneration/regeneration, or visual function. These experimental results provide a physiologic underpinning for the lack of efficacy demonstrated in a large trial of MP treatment of clinical optic nerve injury.
authors.affiliation: Department of Clinical Neuroscience, Section of Neurosurgery, Karolinska Institute and Hospital, Stockholm, Sweden. marcus.ohlsson@ks.se
authors.forename: Marcus
authors.initials: M
authors.lastname: Ohlsson
authors.forename: Ulf
authors.initials: U
authors.lastname: Westerlund
authors.forename: Iver A
authors.initials: IA
authors.lastname: Langmoen
authors.forename: Mikael
authors.initials: M
authors.lastname: Svensson
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000648:ultrastructure; D053331:Ectodysplasins; D005074:Evoked Potentials, Visual / Q000187:drug effects; D005260:Female; D005452:Fluoresceins; D005456:Fluorescent Dyes; D019922:GAP-43 Protein / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism; D008775:Methylprednisolone / Q000494:pharmacology*; D009409:Nerve Crush; D009410:Nerve Degeneration / Q000209:etiology / Q000503:physiopathology*; D009416:Nerve Regeneration / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020221:Optic Nerve Injuries / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009930:Organic Chemicals; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000473:pathology; D014949:Wounds, Nonpenetrating / Q000503:physiopathology
chemical_list: D053331:Ectodysplasins; D005452:Fluoresceins; D005456:Fluorescent Dyes; D019922:GAP-43 Protein; D008565:Membrane Proteins; D018696:Neuroprotective Agents; D009930:Organic Chemicals; C435731:fluoro jade; D008775:Methylprednisolone