Genetic influences on secondary degeneration and wound healing following spinal cord injury in various strains of mice

Denise Inman, Lloyd Guth, Oswald Steward

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Various inbred strains of mice exhibit dramatic differences in sensitivity to excitotoxic cell death induced by systemic injections of kainic acid (KA). The present study evaluates whether the same strains are also differentially sensitive to secondary degeneration after spinal cord injury, in which excitotoxic cell death is thought to play a pathogenic role. Spinal cord crush injuries were produced at T9 in two inbred strains that are resistant to KA-induced excitotoxic cell death (C57Bl/6 and Balb/c) and four strains that are sensitive (CD-1, FVB/N, 129T2 Sv/EMS, and C57Bl/10). The spinal cord was prepared for light microscopy at intervals from 1 to 56 days postinjury, and the area of damaged tissue (termed lesion size) and amount of cavitation were determined by quantitative image analysis. Lesion size increased between 1 and 7 days in all strains and then decreased steadily in a wound-healing process that occurs uniquely in mice. The extent of cavitation also gradually decreased from 7 to 56 days in all strains. Although lesion area and cavitation decreased in all strains, there were significant differences in lesion size and cavitation across strains. Specifically, lesion areas in the KA-sensitive strains FVB/N, 129T2 Sv/EMS, and CD-1 were significantly larger at 56 days postinjury than in the KA-resistant strains C57Bl/6 and Balb/c. We conclude that the genetic differences that confer resistance and sensitivity to KA-induced neurotoxicity also modify the secondary degenerative processes that occur after spinal cord injury, so that resistance to excitotoxic injury leads to smaller overall lesions and a more effective wound-healing response.

Original languageEnglish
Pages (from-to)225-235
Number of pages11
JournalJournal of Comparative Neurology
Issue number3
StatePublished - 23 Sep 2002


  • Cell death
  • Excitotoxicity
  • Morphometry
  • Mouse strains
  • Necrosis


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