Cellular changes at the injury site and beyond in response to a moderate contusion to the adult rat spinal cord

Date of Award




Degree Name

Doctor of Philosophy (Ph.D.)

First Committee Member

Patrick M. Wood, Committee Chair

Second Committee Member

Mary B. Bunge, Committee Member


Massive death of neurons, glia, and endothelial cells (ECs) occurs during the first few hours following moderate spinal cord injury (SCI). By 2 days, vessel numbers are decreased, neurons and astrocytes are absent, and only few ED1+ cells (activated macrophages/microglia) are seen in the lesion center. By 7 days, vigorous new vessel growth occurs through the lesion center, but vessel number decreases by 14 days. Additional work was performed to determine: (1) the time course of EC, neuron, astrocyte, and oligodendrocyte death and ED1+ cells/neutrophils infiltration 15 min--48 h after injury, (2) the mode (apoptosis vs. necrosis) of EC death, (3) whether exogenous VEGF and FGF-2 rescues ECs, promotes angiogenesis and tissue sparing. A moderate (10g x 12.5 cm) weight-drop injury was produced in the T8 rat spinal cord and cell types were identified by immunohistochemistry. At the injury site, large neurons decreased 90% at 15 min and were absent at 8 h. ECs died predominantly by necrosis but apoptotic ECs were observed at 1--48 h. EC, neuronal, oligodendrocytic and astrocytic cell death occurred during the first 8 h and preceded ED1+ cells/neutrophils. Neuronal and vessel numbers decreased and ED1+ cells/neutrophils increased after 8 h, 3 mm rostral and caudal to the injury center. A single injection of FGF-2 and VEGF (separately or in combination, 1.0 or 10 mug dose) to the injury site did not improve EC survival, but transient neuronal protection was recorded 3 mm rostral at 24 h (10 mug dose) and at 48 h (1 mug dose). FGF-2 or VEGF (7-day application via mini-pump, 5 mug total dose) promoted angiogenesis caudal to the injury. The results presented here show that the primary injury is established by 8 h and secondary degradative mechanisms occur after 8h 3 mm rostral and caudal to the injury epicenter. In the tissue adjacent to the injury site, exogenous FGF-2 is neuroprotective and ED1+ cells/neutrophils correlated with neuronal death.


Biology, Neuroscience; Biology, Cell

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