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AAV-based gene therapy for axonal regeneration in a rat model of rubrospinal tract lesion

dc.contributor.advisorBähr, Mathias Prof. Dr.
dc.contributor.authorChallagundla, Malleswari
dc.date.accessioned2015-04-29T08:01:40Z
dc.date.available2015-04-29T08:01:40Z
dc.date.issued2015-04-29
dc.identifier.urihttp://hdl.handle.net/11858/00-1735-0000-0022-5FC6-9
dc.identifier.urihttp://dx.doi.org/10.53846/goediss-5040
dc.language.isoengde
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/
dc.subject.ddc570de
dc.titleAAV-based gene therapy for axonal regeneration in a rat model of rubrospinal tract lesionde
dc.typedoctoralThesisde
dc.contributor.refereeBähr, Mathias Prof. Dr.
dc.date.examination2014-05-07
dc.description.abstractengSpinal cord injury (SCI) is a devastating and largely irreversible clinical condition, which can lead to permanent sensory and motor functional disabilities. Worldwide, an estimated 2.5 million people suffer from SCI and more than 130,000 new injuries are reported annually.The mammalian adult CNS is extremely limited in axonal regeneration.Activation of growth impairing pathways by inhibitory extrinsic substrates, scar tissue and a markedly reduced intrinsic growth capacity of adult neurons lead to a severely impaired axonal regeneration, sprouting and functional recovery after spinal cord injury (SCI). The current study was designed to evaluate the potential of AAV-based gene therapy by overexpression of BAG1, reggie1, miRNA-134, or shRNA-mediated downregulation of ROCK2 alone and in combination with an anti-scarring treatment (AST) in an established CNS lesion model, the dorsal spinal cord hemisection. The target molecules were chosen to combine both neuroprotective and pro-regenerative properties and the AST with the iron-chelating agent BPY-DCA was chosen to ameliorate the scar formation further improving axonal regeneration. this study implies that AAV-mediated gene therapy is a highly interesting future therapeutic tool for the treatment of traumatic CNS injuries. BAG1 represents a valuable target, stimulating neuronal survival and collateral sprouting.de
dc.contributor.coRefereeFischer, André Prof. Dr.
dc.contributor.thirdRefereeBrück, Wolfgang Prof. Dr.
dc.contributor.thirdRefereeOuteiro, Tiago Fleming Prof. Dr.
dc.contributor.thirdRefereeDean, Camin Ph.D.
dc.contributor.thirdRefereeHeinrich, Ralf Prof. Dr.
dc.subject.engspinal cord injuryde
dc.subject.engrubrospinal tract
dc.subject.engBAG1
dc.subject.engROCK2
dc.subject.engAdeno associated virus
dc.subject.enggene therapy
dc.subject.engantiscarring treatment
dc.subject.engred nucleus
dc.subject.engaxonal regeneration
dc.subject.engladder rung test
dc.subject.engCatwalk
dc.subject.engmotor behavioral test
dc.subject.engopen field test
dc.identifier.urnurn:nbn:de:gbv:7-11858/00-1735-0000-0022-5FC6-9-8
dc.affiliation.instituteGöttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB)de
dc.subject.gokfullBiologie (PPN619462639)de
dc.identifier.ppn823756440


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