Distinct roles of endogenous vascular endothelial factor receptor 1 and 2 in neural protection after spinal cord injury

Munehisa Shinozaki, Masaya Nakamura, Tsunehiko Konomi, Yoshiomi Kobayashi, Morito Takano, Nobuhito Saito, Yoshiaki Toyama, Hideyuki Okano

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Secondary degeneration after spinal cord injury (SCI) is caused by increased vascular permeability, infiltration of inflammatory cells, and subsequent focal edema. Therapeutic interventions using neurotrophic factors have focused on the prevention of such reactions to reduce cell death and promote tissue regeneration. Vascular endothelial growth factor (VEGF) is a potent angiogenic and vascular permeability factor. However, the effect of VEGF on SCI remains controversial. VEGF signaling is primarily regulated through two primary receptors, VEGF receptor 1 (VEGF-R1) and VEGF receptor 2 (VEGF-R2). The purpose of this study was to examine the effects of intraperitoneal administration of VEGF-R1- and VEGF-R2-neutralizing antibodies on a mouse model of SCI. VEGF-R1 blockade, but not VEGF-R2 blockade, decreased the permeability and infiltration of inflammatory cells, and VEGF-R2 blockade caused a significant increase in neuronal apoptosis in the acute phase of SCI. VEGF-R2 blockade decreased the residual tissue area and the number of neural fibers in the chronic phase of SCI. VEGF-R2 blockade worsened the functional recovery and prolonged the latency of motor evoked potentials. These data suggest that endogenous VEGF-R2 plays a crucial role in neuronal protection after SCI.

Original languageEnglish
Pages (from-to)55-64
Number of pages10
JournalNeuroscience Research
Volume78
Issue number1
DOIs
Publication statusPublished - 2014 Jan

Keywords

  • Functional recovery
  • Neurotrophic factor
  • Spinal cord injury
  • Vascular endothelial growth factor
  • Vascular endothelial growth factor receptor

ASJC Scopus subject areas

  • Neuroscience(all)

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