Angiogenesis occurs in response to traumatic spinal cord injury (SCI). However, the role of angiogenesis in SCI is controversial. Based on our preliminary in vivo longitudinal magnetic resonance imaging (MRI), neurobehavioral, and end point histology studies, we hypothesize that angiogenesis is beneficial to recovery from SCI. We propose to verify this hypothesis by modulating the angiogenic activity by acute and long term administration of vascular endothelial growth factor (VEGF; for promoting angiogenesis) and anti-VEGF (neutralizing the effects of endogenous VEGF) in experimental SCI. The effect of these compounds will be assessed by combining in vivo longitudinal multi-modal magnetic resonance imaging (MRI) with immunohistochemical studies and neurobehavioral studies. The multi-modal MRI studies include high resolution anatomical, diffusion tensor imaging (DTI), magnetization transfer imaging (MTI), perfusion imaging, and dynamic contrast enhanced MRI (DCE MRI). DTI and MTI will be used to probe the integrity of fiber tracts while DCE MRI and perfusion MRI will allow us to identify and characterize the neovasculature, determine the vascular density, and map the blood-spinal cord permeability. Sophisticated image processing techniques will be implemented for generating and displaying the neovasculature. The temporal changes in the endogenous VEGF expression and its correlation with angiogenic activity following SCI will be investigated for interpreting the MRI results on a rational basis. Detailed immunohistochemical studies will be performed for identifying neovasculature. The MRI measures will be correlated with neurobehavioral scores If the role of angiogenesis in recovery from SCI is confirmed, it should be possible to treat SCI subjects with drugs that manipulate the angiogenic activity to augment the endogenous repair processes. In addition, it is possible to modulate angiogenesis in conjunction with other treatments, such as cellular grafts to further enhance the recovery from SCI. Thus the proposed studies have a very high degree of clinical relevance. ? ?
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