Neutralizing Endogenous VEGF Following Traumatic Spinal Cord Injury Modulates Microvascular Plasticity but not Tissue Sparing or Functional Recovery

Curr Neurovasc Res, 2009 · DOI: · Published: May 1, 2009

Spinal Cord Injury Cardiovascular Science Neurology

Simple Explanation

Traumatic spinal cord injury (SCI) leads to loss of blood vessels and an angiogenic response that causes microvascular dysfunction. This study investigates the role of endogenous VEGF, a potent vasoactive factor, in this process. The researchers used a VEGF Trap to neutralize VEGF in mice with SCI. They then examined the effects on blood vessel plasticity, tissue damage, and functional recovery. The study found that blocking endogenous VEGF altered blood vessel characteristics, but did not improve tissue sparing or functional recovery after SCI.

Study Duration

6 Weeks

Participants

26 adult female C57Bl/6 mice

Evidence Level

Not specified

Key Findings

1
VEGF Trap treatment did not alter total vascularity in the injury epicenter or penumbral zones, suggesting that VEGF is not essential for SCI-induced neovascularization.
2
Significantly more regenerated blood vessels expressed luminal affinity for IB4, indicating that endogenous VEGF modulates endothelial cell plasticity post-SCI.
3
Neutralizing endogenous VEGF did not attenuate or exacerbate chronic histopathology or functional recovery following SCI.

Research Summary

This study investigated the role of endogenous VEGF in microvascular responses and functional recovery following traumatic spinal cord injury (SCI) in mice. The researchers found that neutralizing endogenous VEGF modulated microvascular plasticity, specifically increasing IB4 binding in regenerated blood vessels, but did not affect overall vascular density. The study concluded that endogenous VEGF is neither neuroprotective nor detrimental following traumatic SCI and that angiogenesis in injured spinal tissue is regulated by multiple factors.

Practical Implications

Complexity of Vascular Regulation

Highlights the intricate molecular control of micro-vascular responses to SCI, suggesting that single-molecule targeting may be insufficient for therapeutic intervention.

Combinatorial Therapeutic Approaches

Suggests that future therapies should involve combinatorial approaches targeting multiple molecular effectors of pathoangiogenesis, including VEGF signaling, to stabilize and improve microvascular function in CNS pathology.

Potential for Isoform-Specific VEGF Targeting

Indicates that VEGF's role in vascular remodeling after SCI may be isoform-specific, warranting further investigation into the distinct effects of different VEGF isoforms.

Study Limitations

1
The study focused on a single time point for assessing acute microvascular plasticity (7 days post-SCI).
2
The study used a specific VEGF Trap (Aflibercept), and the results may not be generalizable to other VEGF inhibitors.
3
The study was conducted in mice, and the findings may not directly translate to humans with SCI.

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