Effect of VEGF treatment on the blood-spinal cord barrier permeability in experimental spinal cord injury: dynamic contrast-enhanced magnetic resonance imaging.
Compromised blood-spinal cord barrier (BSCB) is a factor in the outcome following traumatic spinal cord injury (SCI). Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis and vascular permeability. The role of VEGF in SCI is controversial. Relatively little is known about the spatial and temporal changes in the BSCB permeability following administration of VEGF in experimental SCI. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) studies were performed to noninvasively follow spatial and temporal changes in the BSCB permeability following acute administration of VEGF in experimental SCI over a post-injury period of 56 days. The DCE-MRI data was analyzed using a two-compartment pharmacokinetic model. Animals were assessed for open field locomotion using the Basso-Beattie-Bresnahan score. These studies demonstrate that the BSCB permeability was greater at all time points in the VEGF-treated animals compared to saline controls, most significantly in the epicenter region of injury. Although a significant temporal reduction in the BSCB permeability was observed in the VEGF-treated animals, BSCB permeability remained elevated even during the chronic phase. VEGF treatment resulted in earlier improvement in locomotor ability during the chronic phase of SCI. This study suggests a beneficial role of acutely administered VEGF in hastening neurobehavioral recovery after SCI.
Patel
Chirag B
CB
Department of Diagnostic and Interventional Imaging, University of Texas Medical School at Houston, Houston, Texas 77030, USA.
Cohen
David M
DM
Ahobila-Vajjula
Pallavi
P
Sundberg
Laura M
LM
Chacko
Tessy
T
Narayana
Ponnada A
PA
D000704:Analysis of Variance; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D008954:Models, Biological; D009043:Motor Activity; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism* / Q000627:therapeutic use
D042461:Vascular Endothelial Growth Factor A