AAV-KLF7 Promotes Descending Propriospinal Neuron Axonal Plasticity after Spinal Cord Injury

Abstract

DPSN axons mediate and maintain a variety of normal spinal functions. Unsurprisingly, DPSN tracts have been shown to mediate functional recovery following SCI. KLF7 could contribute to CST axon plasticity after spinal cord injury. In the present study, we assessed whether KLF7 could effectively promote DPSN axon regeneration and synapse formation following SCI. An AAV-KLF7 construct was used to overexpress KLF7. In vitro, KLF7 and target proteins were successfully elevated and axonal outgrowth was enhanced. In vivo, young adult C57BL/6 mice received a T10 contusion followed by an AAV-KLF7 injection at the T7–9 levels above the lesion. Five weeks later, overexpression of KLF7 was expressed in DPSN. KLF7 and KLF7 target genes (NGF, TrkA, GAP43, and P0) were detectably increased in the injured spinal cord. Myelin sparring at the lesion site, DPSN axonal regeneration and synapse formation, muscle weight, motor endplate morphology, and functional parameters were all additionally improved by KLF7 treatment. Our findings suggest that KLF7 promotes DPSN axonal plasticity and the formation of synapses with motor neurons at the caudal spinal cord, leading to improved functional recovery and further supporting the potential of AAV-KLF7 as a therapeutic agent for spinal cord injury.

Combinatory transplantation of mesenchymal stem cells with flavonoid small molecule in acellular nerve graft promotes sciatic nerve regeneration

“…In our recent study, BMSCs engineered to overexpress Krüppel-like Factor 7 (KLF7) improved axon regeneration and repair of the injured nerve when injected into an ANA for engraftment into the injured nerve 3 and KLF7 also promotes such benefits in central nervous system injury. [34][35][36] Prior to this, we found that Schwann cells transfected to over express KLF7, and KLF7 in general, also imparted benefits for successful repair and regeneration of the sciatic nerve following engraftment. 34,35 Through our studies, and those of others, the mechanism by which KLF7 promoted these benefits likely involved increased neurotrophic factor expression, growth cone formation, and axonal myelination.…”

Resveratrol treatment of spinal cord injury in rat model

“…Current research has shown GAP43 to be a known marker in detecting nerve regeneration (Li et al, ). GAP43 is mainly involved in sprouting and regeneration of mature axons in their phosphorylated form.…”

Propriospinal Neurons: Essential Elements of Locomotor Control in the Intact and Possibly the Injured Spinal Cord

“…Application of BDNF to the left motor cortex after a thoracic over-hemisection in mice caused collateral sprouting of injured CST axons and formation of contacts with propriospinal INs that was accompanied by functional recovery (Vavrek et al, 2006). In another study, the transduction of the transcription factor Kruppel-like factor 7 (KLF7) by an AAV vector above the injury site after a T10 contusion was shown to promote both descending propriospinal axon plasticity and synapse formation after a T10 contusion in adult mice (Li et al, 2017). KLF7 regulates the expression of a number of genes, including the neurotrophin NGF and its receptor TrkA (Caiazzo et al, 2010).…”