Effects Of Neuroglial Cell On Nerve Regeneration After Spinal Cord Injury

A hostile environment,such as myelin- or glial scar-associated inhibitors and the glial scar in the lesion,and decreased regenerative capacity may contribute to the failure of axon regeneration after spinal cord injury(SCI).Currently,olfactory ensheathing cells (OECs) transplantation has emerged as a very promising experimental therapy to treat SCI.In the present study,our purpose is to explore the effects of OECs and Astrocytes on neural regeneration after SCI and the underlying mechanisms.Our studies indicated that:(1) Glial cell line-derived neurotrophic factor(GDNF) promotes OECs migration via GFRα-1 and Ret regulation of JNK and Src both in vivo and in vitro.(2) Nogo,a myelin-associated inhibitor of axon regeneration in the CNS,enhances the adhesion and inhibits the migration of OECs via RhoA activation by NgR.(3) TNF-αproduced by reactive astrocytes in glial scar attracts OECs migration via TNFR1 regulation of ERK.(4) LLDT-2,a triptolide derivative,inhibits the activation astrocytes and the formation of glial scar,which contributes to axon regeneration and functional recovery after SCI.(5) Differentially expressed genes including Anxa2,Cdh11,Fn1,Lmbr11 and Efna5 were found in the olfactory bulb following olfactory bulb transection.Some of these genes may play a role in directing the regenerated olfactory nerve to olfactory bulb,sorting of olfactory nerve in olfactory bulb,targeting neurotrophy for ORNs,and migration of OECs from olfactory epithelium to olfactory bulb.All these works will be beneficial for us to understand the mechanisms of repair after SCI and as a significant cue to open new avenues for treating SCI.