title: Radiation response of the rat cervical spinal cord after irradiation at different ages: tolerance, latency and pathology.
abstract: OBJECTIVE
  The investigation of the age dependent single-dose radiation tolerance, latency to radiation myelopathy, and the histopathological changes after irradiation of the rat cervical spinal cord.
  
  
  METHODS
  Rats, ages 1-18 weeks, were irradiated with graded single doses of 4 MV photons to the cervical spinal cord. When the rats showed definite signs of paresis of the forelegs, they were killed and processed for histological examination.
  
  
  RESULTS
  The radiation dose in paresis due to white matter damage in 50% of the animals (ED50) after single dose irradiation was about 21.5 Gy at all ages > or = 2 weeks (mean 21.4 (mean 21.4 Gy; 95% CI 21.0, 21.7 Gy). Only the ED50 at 1 week was significantly lower (19.5 Gy; 18.7, 20.3 Gy). The latency to the development of paresis clearly changed with the age at irradiation, from about 2 weeks after irradiation at 1 week to 6-8 months after irradiation at age > or = 8 weeks. The white matter damage was similar in all symptomatic animals studied. The most prominent were areas with diffuse demyelination and swollen axons, often with focal necrosis, accompanied by glial reaction. This was observed in all symptomatic animals, irrespective of the age at irradiation. Expression of vascular damage appeared to depend on the age at irradiation. No vascular damage was observed in the rats irradiated at 1 week, clearly altered blood vessels were seen in animals symptomatic 10 weeks after irradiation at > or = 3 weeks, and vascular necrosis occurred after > or = 6 months in some rats irradiated at > or = 8 weeks.
  
  
  CONCLUSIONS
  Although the latency to myelopathy is clearly age dependent, single dose tolerance is not age dependent at age > or = 2 weeks in the rat cervical spinal cord. The white matter damage is similar in all symptomatic animals studied, but the vasculopathies appear to be influenced by the age at irradiation. It is concluded that white matter damage and vascular damage are separate phenomena contributing to the development of radiation myelopathy, expression of which may depend on the radiation dose applied and the age at irradiation.
authors.affiliation: Institute of Radiotherapy, University of Nijmegen, The Netherlands.
authors.forename: A C
authors.initials: AC
authors.lastname: Ruifrok
authors.forename: L C
authors.initials: LC
authors.lastname: Stephens
authors.forename: A J
authors.initials: AJ
authors.lastname: van der Kogel
mesh_terms: D000367:Age Factors; D000818:Animals; D004307:Dose-Response Relationship, Radiation; D005260:Female; D009333:Neck; D010291:Paresis / Q000209:etiology*; D011833:Radiation Injuries, Experimental / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D013116:Spinal Cord / Q000473:pathology / Q000528:radiation effects*; D013997:Time Factors