کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6017685 | 1580171 | 2014 | 16 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A comparative morphological, electrophysiological and functional analysis of axon regeneration through peripheral nerve autografts genetically modified to overexpress BDNF, CNTF, GDNF, NGF, NT3 or VEGF
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
عصب شناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The clinical outcome of microsurgical repair of an injured peripheral nerve with an autograft is suboptimal. A key question addressed here is: can axon regeneration through an autograft be further improved? In this article the impact of six neurotrophic factors (BDNF, CNTF, GDNF, NGF, NT3 or VEGF) on axon regeneration was compared after delivery to a 1Â cm long nerve autograft by gene therapy. To distinguish between early and late effects, regeneration was assessed at 2 and 20Â weeks post-surgery by histological, electrophysiological and functional analysis. BDNF, GDNF and NGF exhibited a spectrum of effects, including early stimulatory effects on axons entering the autograft and excessive axon growth and Schwann cell proliferation at 20Â weeks post-surgery. Persistent expression of these factors in autografts interfered with target cell reinnervation and functional recovery in a modality specific way. Autografts overexpressing VEGF displayed hypervascularization, while grafts transduced with CNTF and NT3 were indistinguishable from control grafts. These three factors did not have detectable pro-regenerative effects. In conclusion, autograft-based repair combined with gene therapy for three of the six growth factors investigated (BDNF, GDNF, NGF) showed considerable promise since these factors enhanced modality specific axon outgrowth in autografts. The remarkable and selective effects of BDNF, GDNF and NGF on motor or sensory regeneration will be exploited in future experiments that aim to carefully regulate their temporal and spatial expression since this has the potential to overcome the adverse effects on long-distance regeneration observed after uncontrolled delivery.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Neurology - Volume 261, November 2014, Pages 578-593
Journal: Experimental Neurology - Volume 261, November 2014, Pages 578-593
نویسندگان
Stefan A. Hoyng, Fred De Winter, Sara Gnavi, Ralph de Boer, Lennard I. Boon, Laura M. Korvers, Martijn R. Tannemaat, Martijn J.A. Malessy, Joost Verhaagen,