Neuronal overexpression of tissue-type plasminogen activator does not enhance sensory axon regeneration or locomotor recovery following dorsal hemisection of adult mouse thoracic spinal cord

Lawrence D F Moon, R. Madani, J. D. Vassalli, Mary B Bunge

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

CNS axons rarely regenerate spontaneously back to original targets following spinal cord injury (SCI). Neuronal expression of the serine protease tissue-type plasminogen activator (tPA) enhances axon growth in vitro and following PNS injury. Here we test the hypothesis that neuronal overexpression of tPA in adult transgenic mice promotes CNS axon regeneration and functional recovery following SCI. Adult wild-type and transgenic mouse spinal cords were subjected to dorsal hemisection at the level of the T10/T11 vertebrae. PCR confirmed incorporation of the transgene. Immunolabeling revealed overexpression of tPA in transgenic mice in neurons, including large-diameter neurons in lumbar dorsal root ganglia that contribute axons to the dorsal columns, Immunolabeling also revealed the presence of tPA protein within axons juxtaposing the injury site in transgenics but not wild types. In situ zymography revealed abundant enzymatic activity of tPA in gray matter of thoracic spinal cords of transgenics but not wild types. Rotorod locomotor testing revealed no differences between groups in locomotor function up to 21 days postinjury. Transganglionic tracer was injected into the crushed right sciatic nerve 28 days postinjury, and mice were killed 3 days later. There was no evidence for regrowth of ascending dorsal column sensory axons through or beyond the injury site. In conclusion, despite neuronal overexpression of tPA in injured neurons of transgenics, neither locomotor recovery nor regeneration of ascending sensory axons was observed following thoracic dorsal hemisection.

Original languageEnglish
Pages (from-to)1245-1254
Number of pages10
JournalJournal of Neuroscience Research
Volume84
Issue number6
DOIs
StatePublished - Nov 1 2006

Fingerprint

Tissue Plasminogen Activator
Axons
Regeneration
Spinal Cord
Plasminogen Activators
Thorax
Transgenic Mice
Spinal Cord Injuries
Neurons
Wounds and Injuries
Spinal Ganglia
Serine Proteases
Sciatic Nerve
Transgenes
Spine
Polymerase Chain Reaction
Growth
Proteins

Keywords

  • Proteolysis
  • Serine protease
  • Spinal cord injury
  • Transgenic

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Neuronal overexpression of tissue-type plasminogen activator does not enhance sensory axon regeneration or locomotor recovery following dorsal hemisection of adult mouse thoracic spinal cord. / Moon, Lawrence D F; Madani, R.; Vassalli, J. D.; Bunge, Mary B.

In: Journal of Neuroscience Research, Vol. 84, No. 6, 01.11.2006, p. 1245-1254.

Research output: Contribution to journalArticle

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