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 language | English |
|---|---|
| Pages (from-to) | 55-64 |
| Number of pages | 10 |
| Journal | Neuroscience Research |
| Volume | 78 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2014 Jan |
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Keywords
- Functional recovery
- Neurotrophic factor
- Spinal cord injury
- Vascular endothelial growth factor
- Vascular endothelial growth factor receptor
ASJC Scopus subject areas
- Neuroscience(all)
- Medicine(all)
Cite this
Distinct roles of endogenous vascular endothelial factor receptor 1 and 2 in neural protection after spinal cord injury. / Shinozaki, Munehisa; Nakamura, Masaya; Konomi, Tsunehiko; Kobayashi, Yoshiomi; Takano, Morito; Saito, Nobuhito; Toyama, Yoshiaki; Okano, Hideyuki.
In: Neuroscience Research, Vol. 78, No. 1, 01.2014, p. 55-64.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Distinct roles of endogenous vascular endothelial factor receptor 1 and 2 in neural protection after spinal cord injury
AU - Shinozaki, Munehisa
AU - Nakamura, Masaya
AU - Konomi, Tsunehiko
AU - Kobayashi, Yoshiomi
AU - Takano, Morito
AU - Saito, Nobuhito
AU - Toyama, Yoshiaki
AU - Okano, Hideyuki
PY - 2014/1
Y1 - 2014/1
N2 - 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.
AB - 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.
KW - Functional recovery
KW - Neurotrophic factor
KW - Spinal cord injury
KW - Vascular endothelial growth factor
KW - Vascular endothelial growth factor receptor
UR - http://www.scopus.com/inward/record.url?scp=84892674861&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84892674861&partnerID=8YFLogxK
U2 - 10.1016/j.neures.2013.09.011
DO - 10.1016/j.neures.2013.09.011
M3 - Article
C2 - 24107617
AN - SCOPUS:84892674861
VL - 78
SP - 55
EP - 64
JO - Neuroscience Research
JF - Neuroscience Research
SN - 0168-0102
IS - 1
ER -