Application of the sodium hyaluronate-CNTF scaffolds in repairing adult rat spinal cord injury and facilitating neural network formation

Abstract

The present study aimed to explore the potential of the sodium hyaluronate-CNTF (ciliary neurotrophic factor) scaffold in activating endogenous neurogenesis and facilitating neural network re-formation after the adult rat spinal cord injury (SCI). After completely cutting and removing a 5-mm adult rat T8 segment, a sodium hyaluronate-CNTF scaffold was implanted into the lesion area. Dil tracing and immunofluorescence staining were used to observe the proliferation, differentiation and integration of neural stem cells (NSCs) after SCI. A planar multielectrode dish system (MED64) was used to test the electrophysiological characteristics of the regenerated neural network in the lesioned area. Electrophysiology and behavior evaluation were used to evaluate functional recovery of paraplegic rat hindlimbs. The Dil tracing and immunofluorescence results suggest that the sodium hyaluronate-CNTF scaffold could activate the NSCs originating from the spinal cord ependymal, and facilitate their migration to the lesion area and differentiation into mature neurons, which were capable of forming synaptic contact and receiving glutamatergic excitatory synaptic input. The MED64 results suggest that functional synapsis could be established among regenerated neurons as well as between regenerated neurons and the host tissue, which has been evidenced to be glutamatergic excitatory synapsis. The electrophysiology and behavior evaluation results indicate that the paraplegic rats' sensory and motor functions were recovered in some degree. Collectively, this study may shed light on paraplegia treatment in clinics.

Neurogenesis as a Tool for Spinal Cord Injury

“…As this approach was successful it was also repeated in monkeys with a hemisection model of SCI, where it led to neuroregeneration, the growth of cortico-spinal tract (CST) axons through the lesion and functional recovery [ 67 ]. A sodium hyaluronate scaffold was combined with a ciliary neurotrophic factor [ 68 ]. In this study, a scaffold with neurotrophic factor was implanted into a 5 mm gap after the removal of a 5 mm T8 segment of a spinal cord in rats.…”

“…In this study, a scaffold with neurotrophic factor was implanted into a 5 mm gap after the removal of a 5 mm T8 segment of a spinal cord in rats. The scaffold releasing ciliary neurotrophic factor (CNTF) led to the activation of endogenous SCECs, their migration to the injury site, differentiation into neurons and even the formation of functional synapses, followed by the improvement of motor and sensory functions [ 68 ]. Injectable hydrogels can fill the lesion cavities and, therefore, appropriately integrate into the tissue and modify the environment for better regeneration [ 69 , 70 ].…”

Research progress of endogenous neural stem cells in spinal cord injury

“…The results suggest that endogenous CNTF regulates adult neurogenesis by increasing the proliferation of neural stem cells and/or precursors. Besides, the sodium hyaluronate—CNTF scaffold can activate ENSCs, and help them form glutamate‐excitatory functional synapses 48 …”

Bio-Scaffolds as Cell or Exosome Carriers for Nerve Injury Repair

“…Long-chain HA is essential for supporting ECM components of different molecular weights in vivo [39]. An HA scaffold containing ciliary neurotrophic factor stimulated endogenous neurogenesis and facilitated neural-network formation, synaptogenesis, and motor recovery following T8 spinal cord transection in rodents [40].…”