Effect of VEGF Treatment on the Blood-Spinal Cord Barrier Permeability in Experimental Spinal Cord Injury: Dynamic Contrast-Enhanced Magnetic Resonance Imaging

Abstract

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.

The Dual Cyclooxygenase/5-Lipoxygenase Inhibitor Licofelone Attenuates P-Glycoprotein-Mediated Drug Resistance in the Injured Spinal Cord

“…Patel and colleagues have previously demonstrated BSCB dysfunction in the chronic phase of SCI, as evidenced by enhanced vascular permeability within the lesion site, and in spinal cord tissue away from the epicenter of injury, for up to 8 weeks postinjury. 107 Together with these findings, our observations of progressive alterations in Pgp expression suggest the presence of a progressive, spreading BSCB pathology that encompasses both ''active'' as well as ''passive'' components of barrier function. As BSCB integrity may be an important determinant of functional outcome following SCI, 105 further investigation is needed in order to gain a better understanding of the progression of vascular changes following SCI.…”

Sustained Expression of Vascular Endothelial Growth Factor and Angiopoietin-1 Improves Blood–Spinal Cord Barrier Integrity and Functional Recovery after Spinal Cord Injury

“…To assess the integrity of the BSCB, contrast-enhanced MRI was performed at 28 and 56 days post-injury, by intravenous administration of the paramagnetic contrast agent gadopentate dimeglumine (Gd, 287 mg/kg, Magnevist; Berlex Laboratories, Montville, NJ) through the implanted vascular access port connected to tubing that was catheterized to the jugular vein as described above Patel et al, 2009;Tofts et al, 1999). The contrast-enhanced data were objectively and quantitatively analyzed in an unbiased manner to estimate the area of enhancement in the injured cord as described elsewhere (Bilgen et al, 2001).…”

“…The compromised spinal cord circulation at the injury site contributes to ischemia and impairs repair processes after injury (Tator, 1991). Previous studies have also demonstrated that disruption of spinal cord blood flow is related to the motor and sensory deficits that result from spinal cord injury (Holtz et al, 1990;Lang-Lazdunski et al, 2000;Patel et al, 2009;Tator and Fehlings, 1991).…”

Effect of Vascular Endothelial Growth Factor Treatment in Experimental Traumatic Spinal Cord Injury:In VivoLongitudinal Assessment

“…VEGF has been investigated in models of spinal cord injury (SCI) and stroke with mixed results. Some studies demonstrated that VEGF treatment resulted in improvement after injury (Facchiano et al, 2002;Patel et al, 2009;Widenfalk et al, 2003), while other studies have found that VEGF treatment exacerbated CNS injury (Benton and Whittemore, 2003;Zhang et al, 2000).…”