Cellular changes at the injury site and beyond in response to a moderate contusion to the adult rat spinal cord
Date of Award
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
Casella, Gizelda Tardin, "Cellular changes at the injury site and beyond in response to a moderate contusion to the adult rat spinal cord" (2002). Dissertations from ProQuest. 1877.