Effect of VEGF on Inflammatory Regulation, Neural Survival, and Functional Improvement in Rats following a Complete Spinal Cord Transection

Abstract

After complete transection of the thoracic spinal segment, neonatal rats exhibit spontaneous locomotor recovery of hindlimbs, but this recovery is not found in adult rats after similar injury. The potential mechanism related to the difference in recovery of neonatal and adult rats remains unknown. In this study, 342 animals were analyzed. The vascular endothelial growth factor (VEGF) level in spinal segments below injury sites was significantly higher in postnatal day 1 rats (P1) compared with 28-day-old adult rats (P28) following a complete T9 transection. VEGF administration in P28 rats with T9 transection significantly improved the functional recovery; by contrast, treatment with VEGF receptor inhibitors in P1 rats with T9 transection slowed down the spontaneous functional recovery. Results showed more neurons reduced in the lumbar spinal cord and worse local neural network reorganization below injury sites in P28 rats than those in P1 rats. Transynaptic tracing with pseudorabies virus and double immunofluorescence analysis indicated that VEGF treatment in P28 rats alleviated the reduced number of neurons and improved their network reorganization. VEGF inhibition in neonates resulted in high neuronal death rate and deteriorated network reorganization. In in vivo studies, T9 transection induced less increase in the number of microglia in the spinal cord in P1 animals than P28 animals. VEGF treatment reduced the increase in microglial cells in P28 animals. VEGF administration in cultured spinal motoneurons prevented lipopolysaccharide (LPS)-induced neuronal death and facilitated neurite growth. Western blots of the samples of lumbar spinal cord after spinal transection and cultured spinal motoneurons showed a lower level of Erk1/2 phosphorylation after the injury or LPS induction compared with that in the control. The phosphorylation level increased after VEGF treatment. In conclusion, VEGF is a critical mediator involved in functional recovery after spinal transection and can be considered a potential target for clinical therapy.

Apolipoprotein E Deficiency Exacerbates Spinal Cord Injury in Mice: Inflammatory Response and Oxidative Stress Mediated by NF-κB Signaling Pathway

“…As the section thickness is 20 μm, it can be inferred that there are 15 sections in the 300 μm range. Neurons with a clear nucleolus and a Nissl bodies were counted by using previously published methods (Li et al, 1994 ; Li J. et al, 2017 ). According to Rexed’s lamina system of gray matter, the mean number of ventral motor neurons on two sides (lamina IX) was manually calculated through ImageJ2x software.…”

Cell Secretome: Basic Insights and Therapeutic Opportunities for CNS Disorders

“…As such, VEGF fosters the reorganization of the spinal motor network after SCI [71] and also underlies a protective effect against ischemia [69]. Among currently known neurotrophic factors, GDNF has the most pronounced neuroprotective effect, which is particularly relevant in ischemic brain damage [72,73] and neurodegenerative diseases [74][75][76]. The effects of GDNF on GluR2-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors reduce the postsynaptic membrane permeability to calcium ions, which may be considered a possible mechanism for protecting neural cells from hypoxic damage [73].…”

Epigallocatechin gallate enhances the motor neuron survival and functional recovery after brachial plexus root avulsion by regulating FIG4

“…The primary culture of MNs was performed according to the previous studies with mirror modifications [6,20,23,40]. The spinal cord tissues from 0-day mice pups were dissected on the ice, and then digested with Hank's balanced salt solution (HBSS; 14175079, Thermo Fisher Scientific) containing 0.125% trypsin (25200056, Thermo Fisher Scientific) for 20 min at 37°C, 5% CO 2 atmosphere.…”

“…Cell viability assay was performed according to the previous studies with minor modifications [5,23]. The Cell Counting Kit (CCK-8; HY-K0301, MedChem Express, China) was used to evaluate cell viability.…”