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.

Blood-spinal cord barrier permeability in experimental spinal cord injury: dynamic contrast-enhanced MRI.

After a primary traumatic injury, spinal cord tissue undergoes a series of pathobiological changes, including compromised blood-spinal cord barrier (BSCB) integrity. These vascular changes occur over both time and space. In an experimental model of spinal cord injury (SCI), longitudinal dynamic contrast-enhanced MRI (DCE-MRI) studies were performed up to 56 days after SCI to quantify spatial and temporal changes in the BSCB permeability in tissue that did not show any visible enhancement on the post-contrast MRI (non-enhancing tissue). DCE-MRI data were analyzed using a two-compartment pharmacokinetic model. These studies demonstrate gradual restoration of BSCB with post-SCI time. However, on the basis of DCE-MRI, and confirmed by immunohistochemistry, the BSCB remained compromised even at 56 days after SCI. In addition, open-field locomotion was evaluated using the 21-point Basso-Beattie-Bresnahan scale. A significant correlation between decreased BSCB permeability and improved locomotor recovery was observed.

Histological correlation of diffusion tensor imaging metrics in experimental spinal cord injury.

Diffusion tensor imaging (DTI) has the potential to provide important information about the integrity of white matter tracts in injured spinal cord tissue. It is thought that DTI-based transverse diffusivity (lambda(t)) reflects the state of myelin, whereas longitudinal diffusivity (lambda(l)) reflects axonal integrity. However, this has not been established in spinal cord injury (SCI). Therefore, we performed quantitative histologic analysis on 4- and 8-week post-SCI rodent spinal cords that had received a moderately severe injury at the T7 level and correlated the histology with lambda(t) and lambda(l) measured in vivo. Using antibodies specific to myelin and axonal process (i.e., neurofilament), the percent area of expression was determined in the dorsal, ventral, and lateral white matter from both rostral and caudal regions away from the epicenter of the injury site. The results suggest a positive correlation between lambda(t) and demyelination in many but not all regions. However, these studies failed to establish a correlation between lambda(l) and axonal damage. These results suggest that caution must be exercised in interpreting the DTI metrics in terms of tissue pathology in SCI.

Endogenous recovery of injured spinal cord: longitudinal in vivo magnetic resonance imaging.

Pathological changes were followed longitudinally with in vivo magnetic resonance imaging (MRI) and behavioral studies in experimental spinal cord injury (SCI). MRI-observed pathology was correlated with histology. On MRI, the cavitated regions of the injured cord were gradually filled with viable tissue between two and 8 weeks postinjury, and a concomitant improvement was observed in the neurobehavioral scores. By weeks 3-6, on MRI, the gray matter (GM) returned in the segments caudal, but not rostral, to the injury site. The corresponding histological sections revealed motor neurons as well as other nuclei in the gray matter immediately caudal to the epicenter, but not at the site of injury, suggesting neuronal recovery in perilesioned areas. The neuronal and neurological recovery appeared to occur about the same time as neovasculature that was reported on the contrast-enhanced MRI, suggesting a role for angiogenesis in recovery from SCI. The role of angiogenesis in neuronal recovery is further supported by the immunohistochemical observation of greater bromodeoxyuridine uptake by blood vessels near the lesion site compared with uninjured cords.