| Paraplegia below the level of injury resulted from traumatic spinal cord injury (SCI) is one of the tough problems in the world, which is still lack of effective method in clinical treatment. Although the loss of neurons and glial cells in the grey matter at the lesion site can not be ignored, the majority of clinical deficits following SCI results primarily from the severing of long descending and ascending axons in the spinal white matter. Unfortunately, injured axons in the mammalian central nervous system (CNS) do not normally regenerate. In recent years, substantial evidence has suggested that administration of exogenous NTFs into an injured spinal cord can facilitate neuronal growth and recovery. Although the administration of exogenous neurotrophic proteins has therapeutic potential, the limitations imposed by short serum half-life, large molecular weight, high cost and the blood-brain barrier could restrict the clinic utility of this approach. During the past few years, significant progress has been made in the development of techniques for transfecting genes into the SCI and exploring their potential to treat SCI. Glial cell line-derived neurotrophic factor (GDNF), a recently identified and cloned transforming growth factor (TGF)- P super-family trophic factor for midbrain dopaminergic neurons, has been found to support the survival of several neuronal cells including cultured spinal motoneurons and sensory neuron. GDNF is the most potent motor neuron trophic factor among NTFs found so far. There is a hope that GDNF might become useful in the treatment of neurodegenerative diseases and nerve injuries. In present paper, the expression vector of recombinant plasmid pEGFP-GDNF was constructed by using recombinant DNA technology. Then the recombinant plasmid pEGFP-GDNF and cationic liposome complexes were injected into rat thoracic cord in order to investigate the expression of GDNF in the level of transcription and protein. We also used a rat SCI model withcompression inJury according to Nystr6m method. Utilization tbe technique ofHgy fOrward tracing, immunohistochemistry, enzyme histochemistry, Nissl'sstaining and computer image analysis, we observed the effects of GDNF onsurvivaI of spinal cord motoneurons, regeneration of corticospinal tract andfunction recovery of spinal cord locomotor after SCI in adult rats by in vivo genetransfer or intrathecal tubulization.The main results of our research are as fOlIows:l. The recombinant rat GDNF (l0Pglday) was injected into tbe injured regionupon intrathecal tubulization in first week after acute moderate compressedspinaI cord. It was shown that exogenous GDNF reduced motoneurons deathand the changes of cholinesterase (CHE) and acid phosphatase (ACP) activityin lesion cord. These results suggest that exogenous GDNF couId protectmotoneurons from death induced by incompleted spinaI cord injury.2. In order to investigate tbe effect of exogenous GDNF on injured axons andcorticospinal tract regeneration and hindIimbs Iocomotor function recoveryafter severe SCI, The recombinant rat GDNF (l0pg/day) was injected into theinjured region upon intrathecal tubulisation in first week. Four weeks afterSCI, the expression of GFAP and the loss of NF-positive axons in GDNF groupdecreased obviousIy comparing with controI group. Long-distance regenerationof injured corticospinal tract was observed in the caudal spinal cord (up to 0.5cm). The resuIts suggested that exogenous GDNF could reduce the hyperplasiaof gIial ceIIs and enhance the regeneration of injured corticospinal tract andrestoring of the cytoskeleton in the injured neurons. The resuIts of incIinedpIane test and BBB Iocomotor scale showed that exogenous GDNF enhancedIocomotion functionaI restorati...
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