Changes in response to spinal cord injury with development: vascularization, hemorrhage and apoptosis.
Chick embryos are capable of functional spinal cord regeneration following crush injury until embryonic day 13. Developmental changes occurring thereafter result in failure to regenerate. Secondary injury mechanisms can result in apoptotic cell death and make a major contribution to cell loss after trauma. We report here that around embryonic day 13 there is a dramatic increase in blood vessel numbers in the spinal cord, and that the extent of hemorrhage in response to injury increases with developmental age. This is paralleled by increased apoptosis and subsequent cavitation in spinal cords injured at embryonic day 15 as compared with embryonic day 11. Following spinal cord injury at embryonic day 15, apoptotic cell death is extensive and spreads to the same extent as the hemorrhage. When hemorrhage is reduced by treatment with the hemostatic drug desmopressin the extent of apoptosis and cavity formation in spinal cords injured at embryonic day 15 decreases. Furthermore, manipulations of embryonic day 11 spinal cords that increase hemorrhage also increase apoptosis and result in cavitation in contrast to the effective repair typical of this stage. Altogether these results suggest that cavity formation occurring at developmental stages non-permissive for regeneration is largely due to changes in the extent of apoptosis that are related to vascularization and hemorrhage.
Whalley
K
K
Developmental Biology Unit, Institute of Child Health, UCL, 30 Guilford Street, London WC1N 1EH, UK.
O'Neill
P
P
Ferretti
P
P
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002642:Chick Embryo; D003894:Deamino Arginine Vasopressin / Q000378:metabolism / Q000494:pharmacology; D047108:Embryonic Development; D006470:Hemorrhage / Q000473:pathology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D009389:Neovascularization, Pathologic / Q000473:pathology*; D009416:Nerve Regeneration / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000098:blood supply / Q000196:embryology; D013119:Spinal Cord Injuries / Q000473:pathology*
D003894:Deamino Arginine Vasopressin