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

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.

Bosentan protects the spinal cord from ischemia reperfusion injury in rats through vascular endothelial growth factor receptors

“…26 Whereas blocking FLT-1 decreased the infiltration of inflammatory cells, blocking FLK-1 increased neuronal apoptosis and worsened the functional recovery after spinal cord injury, which indicates that FLK-1 plays a crucial neuroprotective role in spinal cord injury. 27 The results of the present study suggested that blocking endothelin receptors by Bosentan increased both FLK-1 and FLT-1 expression, and decreased neuronal apoptosis via possible neurovascular remodeling, including increased angiogenesis and neurogenesis. We would like to evaluate the change in vessel density that is associated with angiogenesis following rat SCIR in later research.…”

A shift of brain network hub after spinal cord injury

“…In this study, significant differences were observed at 7 and 14 weeks after injury. In rodent SCI models, spontaneous recovery of motor function reaches a plateau at 6 weeks ( Supplementary Figure 3 ), which is considered the “chronic phase” ( Shinozaki et al, 2011 , 2014 ). In the brain, however, further changes have been observed from 7 to 14 weeks, with continuous changes from 1 to 14 weeks in macroscopic measures such as mean order centrality, and more fine changes in individual degree centrality.…”

Immunomodulatory and neuroprotective effect of cryopreserved allogeneic mesenchymal stem cells on spinal cord injury in rats

“…A previous study found an increase in the concentration of VEGF in the chronic phase of animals with SCI treated with MSCs . VEGF has direct neuroprotective and neurotrophic actions (Figley et al, 2014;Mead et al, 2014;Shinozaki et al, 2014); therefore, the increase in VEGF expression at 21 days after spinal cord injury in the GMSC may have contributed to a higher number of intact neurons, lower degeneration of white matter, and recovery of motor function.…”