Tissue Transplantation And Neurotrophic Factors On Spinal Cord Injury Repair And Mechanism Study

The Repairing Effects of Different Tissues Transplantation andNeurotrophic Factors on Acute Injured Spinal Cordof Adult Rats and Its MechanismsAbstractSpinal cord injuries (SCI) are generally devastating which can result in loss of function and altered sensation and severe long-term disability and it will cost a financial burden to the victims, their families and the society. Presently, victims of SCI have few remedies for the loss of motor function and the altered sensation. The goal of SCI research is to improve function in both acute and chronic injuries. Until now, there is no breakthrough in the cure of SCI. The main problems are: (1) how to protect the neurons and prevent them from death after SCI; (2) how to promote the regeneration and repair of neural axons; (3) how to reestablish the anatomical connection of injured spinal cord and fulfil functional recovery. A variety of tissues and cells have been transplanted to the adult spinal cord to encourage restoration of function. Among so many interventions, the most successful one is the utilization of transplanted FSC tissues toward improved motor function recovery and reconstructed anatomic connection. The probable mechanisms are that the transplanted tissue could: (1) bridge the spinal lesion and provide chemical and/or mechanical guidance for host neurons to grow across the lesion; (2) bridge the spinal lesion and provide additional cellular elements to repair the damaged circuitry; (3) provide factors that would rescue neurons that would otherwise die and/or modulate neural circuits to improve function. But the survive rate of FSC tissue transplanted into injured spinal cord was very low. In clinical application, there is no one single tissue transplantation can promote the regeneration and repair of neural axons and produce satisfactory motor results in SCJ. So how to establish moreeffective methods and whether the combination methods are more effective ornot should be clarified eXPerimentally.Owing to these reasons, we designed the models using different tissuesand neurotrophic factors (NTFs). The methods included different tissuestransplatation (FSC transplantation plus lesion site pedicle omenialtranspositions; FSC transplantation p1us lesion site pedicle paraspinal muscletYanspositions; FSC transplanation plus lesion site uPper and lower spinalnerve roots anastomosis), Providing NTFs FSC transplantation (FSCtransp1antation plus lesion site apply NTFs); Intraspinal grafting of BDNFencoded by an adenovirus vector (AxCA BDNF) ex vivo transgene myoblastscells and fetal spinal cord. Histopathologic observation, electrophsiologic tests,behavioral tests, immunocytochemistry, in situ hybridization, ['H]MK-801auoradiograPhy and TUNEL reaction were used to investigate the effects andmechanisms of different tissues transplanted and neurotrophic factors onregeneration and repairmeni after SCI. Also by using the teclmique of NTFsexpression, NMDA receptors binding, and aPoptosis detection, we tried toinvestigate the mechanisms of transplamed tissue's repair effects on injuredspinal cord. The main results and conclusions of our experiments are showedas follows:1. Placement of FSC plus pedicle omentum on an acutely injured spinalcord would result in the development of numerous neovascular connectionsbetween these two structllres and a marked increasement of vascular density ininjured spinal cord, which can promote the FSC neurons survive and developto mature. The pedicle parasPinal muscle plus FSC transplamed to injuredspinal cord was futility because along with temporal prolonging, the muscletissues were 1ack of vasclarization that resulted in atrophy fibrosis, and bloodvessel contracture. Four weeks after surgery FSC transplamation plus uPperand lower spinal nerve roots anastomosis provided a bridge connectionIIIbetween upper and lower ending, which could promote the reconstruction ofadult rat injured spinal cord. These models of different tissues transplan...