Angelica Zepeda - Academia.edu (original) (raw)
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Papers by Angelica Zepeda
Journal of Neuropathology and Experimental Neurology, 2007
Vascular endothelial growth factor (VEGF) delays disease onset and progression in transgenic rode... more Vascular endothelial growth factor (VEGF) delays disease onset and progression in transgenic rodent models of familial amyotrophic lateral sclerosis (ALS). Because most cases of ALS are sporadic, it is important to determine whether VEGF can protect motoneurons in a nontransgenic ALS paradigm. We tested this possibility in a new model of chronic excitotoxic spinal neurodegeneration in the rat. Using osmotic minipumps, we continuously infused the glutamate receptor agonist >-amino-3-hydroxy-5methyl-4-isoxazole propionate (AMPA) directly in the lumbar spinal cord. The effect of this treatment on motor behavior was assessed with 3 motor performance tests, and neurodegeneration was evaluated by histologic and immunohistochemical analyses. AMPA infusion produced dose-dependent progressive hindlimb motor deficits, reaching complete bilateral paralysis in~10 days, which was correlated with the loss of spinal motoneurons. VEGF administered together with AMPA completely prevented the motor deficits, and the motoneuron death was reduced by more than 75%. Thus, we have developed an in vivo model of progressive spinal motoneuron death due to overactivation of AMPA receptors. The finding that VEGF protected motoneurons from this AMPA receptor-mediated excitotoxic death suggests that it may be a therapeutic agent in sporadic ALS. FIGURE 5. Chronic infusion of exogenous vascular endothelial growth factor (VEGF) does not alter the vascular architecture of spinal cord. Representative micrographs of rat endothelial cell antigen 1 (RECA-1) immunostaining in lumbar spinal cord of intact rats (control) and in the spinal cord infused with 7.5 mM >-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) + VEGF for 25 days. The RECA-1 pattern is alike in both groups. Lower micrographs are magnifications of the areas in squares in the upper micrographs. Scale bar = 50 Km.
Journal of Neuropathology and Experimental Neurology, 2007
Vascular endothelial growth factor (VEGF) delays disease onset and progression in transgenic rode... more Vascular endothelial growth factor (VEGF) delays disease onset and progression in transgenic rodent models of familial amyotrophic lateral sclerosis (ALS). Because most cases of ALS are sporadic, it is important to determine whether VEGF can protect motoneurons in a nontransgenic ALS paradigm. We tested this possibility in a new model of chronic excitotoxic spinal neurodegeneration in the rat. Using osmotic minipumps, we continuously infused the glutamate receptor agonist >-amino-3-hydroxy-5methyl-4-isoxazole propionate (AMPA) directly in the lumbar spinal cord. The effect of this treatment on motor behavior was assessed with 3 motor performance tests, and neurodegeneration was evaluated by histologic and immunohistochemical analyses. AMPA infusion produced dose-dependent progressive hindlimb motor deficits, reaching complete bilateral paralysis in~10 days, which was correlated with the loss of spinal motoneurons. VEGF administered together with AMPA completely prevented the motor deficits, and the motoneuron death was reduced by more than 75%. Thus, we have developed an in vivo model of progressive spinal motoneuron death due to overactivation of AMPA receptors. The finding that VEGF protected motoneurons from this AMPA receptor-mediated excitotoxic death suggests that it may be a therapeutic agent in sporadic ALS. FIGURE 5. Chronic infusion of exogenous vascular endothelial growth factor (VEGF) does not alter the vascular architecture of spinal cord. Representative micrographs of rat endothelial cell antigen 1 (RECA-1) immunostaining in lumbar spinal cord of intact rats (control) and in the spinal cord infused with 7.5 mM >-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) + VEGF for 25 days. The RECA-1 pattern is alike in both groups. Lower micrographs are magnifications of the areas in squares in the upper micrographs. Scale bar = 50 Km.