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

Abstract

Vascular endothelial growth factor (VEGF) is thought to provide neuroprotection to the traumatically injured spinal cord. We examined whether supplementing the injured environment with VEGF 165 via direct intraspinal injection into the lesion epicenter during the acute phase of spinal cord injury (SCI) results in improved outcome. The effect of treatment was investigated using longitudinal multi-modal magnetic resonance imaging (MRI), neurobehavioral assays, and end-point immunohistochemistry. We observed on MRI that rats treated with VEGF 165 after SCI had increased tissue sparing compared to vehicle-treated animals at the earlier time points. However, these favorable effects were not maintained into the chronic phase. Histology revealed that VEGF 165 treatment resulted in increased oligodendrogenesis and/or white matter sparing, and therefore may eventually lead to improved functional outcome. The increase in spared tissue as demonstrated by MRI, coupled with the possible remyelination and increased neurosensory sensitivity, suggests that VEGF 165 treatment may play a role in promoting plasticity in the sensory pathways following SCI. However, VEGF-treated animals also demonstrated an increased incidence of persistent allodynia, as indicated on the von Frey filament test.

Vascular Pathology as a Potential Therapeutic Target in SCI

“…Such techniques have been developed in other organs, the brain, and in tumors and include non-invasive in vivo blood flow measurements using ultrasound, laser Doppler, laser speckle imaging, near infrared spectroscopy, micro-CT, PET scanning with EC-selective ligands, MRI), real-time multi-photon microscopy, optical frequency domain imaging, and luminosity measurements with fluorescent probes [19,51,93,97,155,156,167,182]. Few groups have access to such equipment and fewer have applied this to spinal cord injury [13,23,24,30,33,39,67,73,126,146,151]. Future combination of newly recognized EC-selective molecular targets will enable the development of even more ligands and methods to non-invasively assess the injured spinal cord.…”

Transplantation of Human Amniotic Mesenchymal Stem Cells Promotes Functional Recovery in a Rat Model of Traumatic Spinal Cord Injury

“…Of the various pro-angiogenic factors, VEGF is reported to play an essential role in promoting angiogenesis, it also exerts a neuroprotective effect and improves cell survival [30]. Exogenous application of VEGF increased the density of blood vessels, decreased cell apoptosis, and improved functional outcome after SCI [31]. Administration of VEGFmodified stem cells enhanced angiogenesis and promoted functional recovery after SCI [32].…”

Biodegradable Cell-Seeded Nanofiber Scaffolds for Neural Repair

“…Widenfalk et al treated SCI in a rat contused spinal cord model with VEGF, and the results showed that VEGF facilitated behavior improvement, increased spared tissue and blood vessel density, and decreased the levels of apoptosis [250]. Sundberg et al also undertook a study on the effect of acute administration of VEGF on SCI repair using a rat model, and they too discovered attenuated cavity formation and increased spared tissue induced by VEGF [30]. In addition, VEGF might facilitate enhancing a permissive environment for axonal regrowth.…”

“…In addition, VEGF might facilitate enhancing a permissive environment for axonal regrowth. However, VEGF might also stimulate plasticity, which might result in chronic pains [30]. On the contrary to the promising results reported by others, Benton et al discovered that VEGF therapy might exacerbate SCI, possibly due to the growth factor-induced microvascular permeability [251].…”

“…However, using empty guidance channels alone hardly produces satisfactory results. Thus, when designing guidance channels made from either hydrogel [18,22,23] or polymer fibers, the following factors require consideration: they should be biodegradable, biocompatible, and permissive for cell growth; include neurostimulatory extracellular matrix (ECM) macromolecules (such as laminin-1 or laminin-1 fragments); include supportive cells, such as Schwann cells and stem cells; and include neurotrophic factors, such as neural growth factor (NGF-See Table 1 for abbreviations of materials in this paper) and brain-derived neurotrophic factor (BDNF) [24][25][26][27][28][29][30][31][32][33][34].…”