Differences In Neurotrophic Factor Gene Expression Profiles And Endogenous Neural Stem Cells Response Between Spinal Cord Of Neonate And Adult Rat

Brachial plexus roots avulsion is a devasteting injury which is charaeterized by the interruption of rootlets from cervical cord and apoptosis or necrosis of spinal cord neurons and always lead to an flaccid arm.Till now,brachial plexus roots avulsion has been treated by neurotization or nerve transposition with some exeiting clinical outeomes.Brachial plexus root avulsion,which always lead to intraspinal neurons apoptosis or necrosis and faild axonal outgrowth with in the non-permisive environment, is considered to be a problem of the central nervous system.The prognosis for brachial plexus injuries is better in children than in adults. Several studies have demonstrated better sensory recovery in children but the exact reason for this is not fully understood. Some believe that it is due to better nerve regeneration in children, while others think it is due to better cerebral plasticity.It has been shown that neurotrophic factors play important roles both in neuronal survival and in axonal elongation during development. More recent studies have also suggested a significant role for neurotrophic factors in regeneration after CNS injury.It was found that NSCs were capable of being activated to proliferation and recruited migration the affected areas.However,the capacity for recruiting endogenous NSCs is limited.The brachial plexus injury mainly divided into the adult brachial plexus injury and pediatric brachial plexus injury.They are different in injury mechanism,recovery and therapeutic principles.In addition to injury mechanisms are different,Whether the differences between cell biology and molecular biology is also the cause for difference of function recovery? The experiment was divided into two parts:1. Differences in neurotrophic factor gene expression profiles between spinal cord of neonate and adult rat Objective:To examine the differences in neurotrophic factor gene expression profiles in spinal cord of neonate and adult rat.Methods:Seven-day-old rat pups and adult rats were subjected to brathial cord injury through posterior subscapular approach.The mRNA of BDNF,NGF and NT-3 was detected by real time PCR analysis at various time points after brathial plexus root injury.The differences of gene expression between neonat rats and adult rats were detected.Results:The neonate rats have the high level of BDNF,NGF,NT-3 expression in 21 days after birth which is far higher than adult rats.The mRNA changes of BDNF,NGF,NT-3 between adult rats and neonate rats were significantly different.The expression levels of BDNF in adult rats were significantly higher than neonate rat in the two weeks after injury (P<0.05). However,the expression levels of BDNF in noenate exceed adult rat in the 21 days after injury(p<0.05).After brachial plexus injury,the expression level of NGF were significantly higher than adult rat (p<0.05) in the 1,14 and 21 days.The expression levels of NT-3 in adult rats were far higher than neonate(p<0.05) during 14 days after injury.Conclusion:This study suggests that:1:Rat model of reimplantation of avulsed root after brachial plexus avulsion had been sueeessfully established through posteriorsubscapular avulsion.2:Target tissue provide neurotrophins to immature neurons to promote the development of neurons.The expression of neurotrophic factors in neonatal spinal cord after birth and decreased gradually with the maturation of neurons.3:Adult rat spinal cord express high levels of neurotrophic factors in the errly stage after injury in order to protect the neurons and stimulate nerve.4:Neonate showed the characteristics different from the adult rat in NTFs expression after brachial plexus root avulsion:The level of NTFs expression was decreased early after injury and increased in the late.2. Differences in endogenous neural stem cells response between spinal cord of neonate and adult ratObjective:To investigate the proliferation and differentiation of endogenous neural stem cells between neonate and adult rat in spinal cord after brachial plexus avulsion and comapare their difference in proliferation and differentiation of endogenous neural stem cells. Methods:Seven-day-old rat pups and adult rats were subjected to brathial cord injury through posterior subscapular approach.BrdU/nestin immunohistochemisty double staining were examined 1,7,14 and 35 days after brachial plexus injury.BrdU/GFAP and BrdU/β-tubulin immunohistochemisty double staining were examined 14 and 35 days after brachial plexus injury.Results:In adult and neonate rats, proliferation of endogenous NSCs was observed in the spinal cord.Cell number of adult rats peaked 14 days after brachial plexus injury,which is different in neonate rats with 7 days.Compared with the neonate rats, the positive cells of BrdU/nestin in adult rats at different time points was significantly higher than that of neonate rats(P<0.05). In adult and neonate rats,BrdU/GFAP positive cells was found peaked 35days after brachial plexus injury.Compared with the neonate rats, the positive cells of BrdU/GFAP in adult rats at different time points was significantly higher than that of neonate rats(P<0.05).Conclusion:This study suggests that:1:brachial plexus root avulsion of adult and neonate rats can cause endogenous neural stem cell proliferation.2:endogenous neural stem cells eventually differentiated into astrocytes.3:Compared with the adult rats, neonate rats have no adwantage in proliferation and differentiation of stem cells caused by brachial plexus root avulsion.4:Compared to adult rats, neonate rats have no advantage in neurogenesis.