کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6018269 | 1580185 | 2013 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Limited regeneration in long acellular nerve allografts is associated with increased Schwann cell senescence
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کلمات کلیدی
GFPSCsDAPIEDLNerve autograft4′,6-diamidino-2-phenylindole - 4 '، 6-دیامیدینو-2-فنیلینولAnas - آناextensor digitorum longus - اکستانسور بلند شست انگشتانSchwann cells - سلول های SchwannPeripheral nerve - عصب محیطیgreen fluorescent protein - پروتئین فلورسنت سبزCellular senescence - پیری سلولیNerve grafting - پیوند عصبی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
عصب شناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Repair of large nerve defects with acellular nerve allografts (ANAs) is an appealing alternative to autografting and allotransplantation. ANAs have been shown to be similar to autografts in supporting axonal regeneration across short gaps, but fail in larger defects due to a poorly-understood mechanism. ANAs depend on proliferating Schwann cells (SCs) from host tissue to support axonal regeneration. Populating longer ANAs places a greater proliferative demand on host SCs that may stress host SCs, resulting in senescence. In this study, we investigated axonal regeneration across increasing isograft and ANA lengths. We also evaluated the presence of senescent SCs within both graft types. A sciatic nerve graft model in rats was used to evaluate regeneration across increasing isograft (~ autograft) and ANA lengths (20, 40, and 60 mm). Axonal regeneration and functional recovery decreased with increased graft length and the performance of the isograft was superior to ANAs at all lengths. Transgenic Thy1-GFP rats and qRT-PCR demonstrated that failure of the regenerating axonal front in ANAs was associated with increased levels of senescence related markers in the graft (senescence associated β-galactosidase, p16INK4A, and IL6). Lastly, electron microscopy (EM) was used to qualitatively assess senescence-associated changes in chromatin of SCs in each graft type. EM demonstrated an increase in the presence of SCs with abnormal chromatin in isografts and ANAs of increasing graft length. These results are the first to suggest that SC senescence plays a role in limited axonal regeneration across nerve grafts of increasing gap lengths.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Neurology - Volume 247, September 2013, Pages 165-177
Journal: Experimental Neurology - Volume 247, September 2013, Pages 165-177
نویسندگان
Maryam Saheb-Al-Zamani, Ying Yan, Scott J. Farber, Daniel A. Hunter, Piyaraj Newton, Matthew D. Wood, Sheila A. Stewart, Philip J. Johnson, Susan E. Mackinnon,