Temporal progression of angiogenesis and basal lamina deposition after contusive spinal cord injury in the adult rat.
After spinal cord injury (SCI), the absence of an adequate blood supply to injured tissues has been hypothesized to contribute to the lack of regeneration. In this study, blood vessel changes were examined in 28 adult female Fischer 344 rats at 1, 3, 7, 14, 28, and 60 days after a 12.5 g x cm NYU impactor injury at the T9 vertebral level. Laminin, collagen IV, endothelial barrier antigen (SMI71), and rat endothelial cell antigen (RECA-1) immunoreactivities were used to quantify blood vessel per area densities and diameters in ventral gray matter (VGM), ventral white matter (VWM), and dorsal columns (DC) at levels ranging 15 mm rostral and caudal to the epicenter. This study demonstrates an angiogenic response, defined as SMI71/RECA-1-immunopositive endothelial cells that colocalize with a robust deposition of basal lamina and basal lamina streamers, 7 days after injury within epicenter VGM. This angiogenesis diminishes concurrent with cystic cavity formation. GAP43- and neurofilament- (68 kDa and 210 kDa) immunopositive fiber outgrowth was associated with these new blood vessels by day 14. Between 28 and 60 days after injury, increases in SMI71-immunopositive blood vessel densities were observed in the remaining VWM and DC with a corresponding increase in vessel diameters up to 15 mm rostral and caudal to the epicenter. This second angiogenesis within VWM and DC, unlike the acute response observed in VGM, did not correspond to any previously described changes in locomotor behaviors in this model. We propose that therapies targeting angiogenic processes be directed at the interval between 3 and 7 days after SCI.
Loy
David N
DN
The MD/PhD Program, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA.
Crawford
Charles H
CH
Darnall
Jessica B
JB
Burke
Darlene A
DA
Onifer
Stephen M
SM
Whittemore
Scott R
SR
D000818:Animals; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000378:metabolism; D001485:Basement Membrane / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001808:Blood Vessels / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D024141:Collagen Type IV / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D019922:GAP-43 Protein / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009416:Nerve Regeneration / Q000502:physiology*; D016900:Neurofilament Proteins / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344 / Q000033:anatomy & histology / Q000293:injuries / Q000378:metabolism*; D020127:Recovery of Function / Q000502:physiology*; D013116:Spinal Cord / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D014945:Wound Healing / Q000502:physiology
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D024141:Collagen Type IV; D019922:GAP-43 Protein; D007797:Laminin; D016900:Neurofilament Proteins; C114781:endothelial barrier antigen, rat