Font Size: a A A

Experimental Study On The Proliferation And Differentiation Of Endogenous Neural Stem/progenitor Cells After Spinal Cord Injury In Rat

Posted on:2009-10-07Degree:MasterType:Thesis
Country:ChinaCandidate:F GaoFull Text:PDF
GTID:2144360272961851Subject:Bone surgery
Abstract/Summary:PDF Full Text Request
Spinal cord injury (SCI) is a kind of extremely severe damage that having high disability rate. The traditional treatment to SCI usually included spine fracture -dislocation stabilization, relieve spinal cord compression, symptom therapy and rehabilitative treatment. On recent, following development of study of neuro-pathophysiology and auxology, conventional idea that nervous tissue do not regenerative had challenged. The discover and confirm of Neural stem cells have brought a new way for intractable diseases of center neural system including SCI.Neural stem cells(NSCs) are a kind of cells that have the ability to differentiate into neurons, astrocytes and oligodendrocytes. They have self-renewal activity and multi-potential proliferation, which is important for theory research and clinical applications. The transplantation of a variety of cells, particularly the neural stem cells or NPCs, in multiple central nervous system (CNS) injury paradigms has provided to a certain degree encouraging results for functional recovery. While induction and recruitment of endogenous adult NSCs, has received relatively little attention. Compared with transplantation of cells,the activation of endogenous NSCs is use self-resource. It not only get rid of the limit and danger of acquiring NSCs from tissue, but also avoid the exiting questions of ethics , immunological and limited source. It will have a promising future in the treatment of head trauma and degenerative diseases of the central nervous system.Although we have got some progress on neural stem cells, little is knowen about the proliferation, migration, and differentiation of adult NSCs in the mammalian spinal cord, especially the mechanism of regulation in vivo. So used bromodeoxyuridine(BrdU) to label the endogenous NSCs in this study,we study the proliferation and differentiation of endogenous neural stem/progenitor cells after spinal cord injury in rat. In addition, WNT-1 has been recently shown to be an important role in the development of central nervous system and in vivo proliferation of NSCs. Therefore, we examined whether exogenous administration of WNT-1 would further increase the numbers of NSCs after SCI in vivo.Partâ… : The proliferation and differentiation of endogenous neural stem/progenitor cells after spinal cord injury in ratObjective: To investigate the effect of endogenous neural stem/progenitor cells after spinal cord injury (SCI) in rats.Methods:(1) Thirty-six female SD rats were randomly divided into three groups:the control group (GroupA), the Brdu-prelabeled group(GroupB) and the Brdu-postlabeled group after SCI(Group C).(2) Animal SCI models were established by Allen method.(3) To label the constitutively proliferating endogenous neural stem/progenitor cells,animals in GroupA and GroupB received one intraperitoneal injection of bromodeoxyuridine (BrdU) each day for 10 days, then Spinal cord injury model was made at 11th day in GroupB. To label the proliferating cells occurs postinjury,Group C received one intraperitoneal injection of BrdU each day for 10 days after SCI.. Animals were euthanized at three timepoints, The tissue was analyzed using immunohistochemical detection to study the response of endogenous neural stem/progenitor cells following SCI.Results: we observed frequent BrdU-positive cells thoughout the spinal cord section in GroupA,they exist in the outer circumference of the spinal cord particularly. Compared with the controls, the number of Brdu positive cells in the GroupB decreased strikingly on the 1st day , increased obviously on the 7st day,returned to normal levels on the 21st day .In Group C, the number of Brdu positive cells increased strikingly on the 1 st day, and excessived compared with that of GroupB , reached maximum and excessived on the 7th day compared with GroupA, these positive cells exist highest in the gray matter adjacent to the lesion and ependymal layer,but there are no more significantly increase on the 21th day. Moreover, compared with GroupA, more nestin expression was observed in ependymal cells on the 1st day after SCI in Group C ,and the peak was occurred at 7th day after injury,decreased. at 21th day.Conclusions: There are endogenous neural stem/progenitor cells in normal adult rats spinal cord, these cells remainin differentiating and dividing, they are vulnerable to injury and lost or significantly reduced after SCI..The spinal cord contains a second neural stem /progenitor cells which slowly multiply, these cells are activated remarkable by injury and rapidly divides to replace the cells lost and participates in the rehabilitation of spinal cord injury.Partâ…¡: Effects on proliferation and differentiation of endogenous neural stem/progenitor cells by administration of WNT-1 after spinal cord injury in rat Objective: To investigate the effect of endogenous neural stem/progenitor cells by administration of WNT-1 after spinal cord injury (SCI) in rats.Methods: Spinal cord injury were made by Allen's method. These rats were randomly divided into the control group (GroupA ) and the WNT-1 group(GroupB), normal saline and WNT-1 were administered via cavitas subarachnoidealis each day for 7 days after SCI. To label the proliferating endogenous neural stem/progenitor cells. Animals received intraperitoneal injection of bromodeoxyuridine (BrdU). Brdu-labeled cells were calculated to characterize neural stem cells at 7d, 14d, 21d after SCI.Results: Brdu-labeled cells were detected in each group after SCI. the number of positive cells decreased progressively. Compared with the control group, the number of Brdu-labeled cells in wnt-1 group increased significantly after treatment. The number of Brdu-labeled cells was maximum at 7d after SCI. Moreover, compared with control group, more nestin expression were observed in ependymal cells on the 7st day after SCI,decreased. at 21th day.Conclusions: The proliferation and differentiation of endogenous neural stem/progenitor cells were stimulated by WNT-1.Conclusion:1.An active endogenous neural stem/progenitor cells involved in spinal cord homeostasis is sensitive to injury and is lost or significantly reduced in response to SCI in rats. This vulnerable population is rapidly replaced by a second, quiescent stem/progenitor population that divides as early as 1d postinjury and reach peak after 1 week.. The activity of proliferation increased obviously after SCI.2. Robust proliferation at 7d postinjury leads to the increased production of new Nestin-positive cells. While the Nestin-positive cells decrease subsequently at 21d postinjury., which prognosticate that it is the important period to manipulate the differentiation in 1w.3.The proliferation and differentiation of endogenous neural stem cells were stimulated by cavitas subar the proliferation and differentiation tion of WNT-1,which indicate that WNT-1 can play active role in SCI.
Keywords/Search Tags:WNT-1, endogenous, stem cells, progenitor Cells, spinal cord injury, Brdu
PDF Full Text Request
Related items