TY  - JOUR
A1  - Costa Oliveira, Karla Mychellyne
A1  - Pindur, Lukas
A1  - Han, Zhihua
A1  - Bhavsar, Mit Balvantray
A1  - Barker, John Howard
A1  - Leppik, Liudmila
T1  - Time course of traumatic neuroma development
T2  - PLoS one
N2  - This study was designed to characterize morphologic stages during neuroma development post amputation with an eye toward developing better treatment strategies that intervene before neuromas are fully formed. Right forelimbs of 30 Sprague Dawley rats were amputated and limb stumps were collected at 3, 7, 28, 60 and 90 Days Post Amputation (DPA). Morphology of newly formed nerves and neuromas were assessed via general histology and neurofilament protein antibody staining. Analysis revealed six morphological characteristics during nerve and neuroma development; 1) normal nerve, 2) degenerating axons, 3) axonal sprouts, 4) unorganized bundles of axons, 5) unorganized axon growth into muscles, and 6) unorganized axon growth into fibrotic tissue (neuroma). At early stages (3 & 7 DPA) after amputation, normal nerves could be identified throughout the limb stump and small areas of axonal sprouts were present near the site of injury. Signs of degenerating axons were evident from 7 to 90 DPA. From day 28 on, variability of nerve characteristics with signs of unorganized axon growth into muscle and fibrotic tissue and neuroma formation became visible in multiple areas of stump tissue. These pathological features became more evident on days 60 and 90. At 90 DPA frank neuroma formation was present in all stump tissue. By following nerve regrowth and neuroma formation after amputation we were able to identify 6 separate histological stages of nerve regrowth and neuroma development. Axonal regrowth was observed as early as 3 DPA and signs of unorganized axonal growth and neuroma formation were evident by 28 DPA. Based on these observations we speculate that neuroma treatment and or prevention strategies might be more successful if targeted at the initial stages of development and not after 28 DPA.
KW  - Axons
KW  - Nerves
KW  - Nerve fibers
KW  - Histology
KW  - Muscle tissue
KW  - Connective tissue
KW  - Nerve regeneration
KW  - Neurobiology of disease and regeneration
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/46975
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-469755
SN  - 1932-6203
N1  - Copyright: © 2018 Oliveira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 13
IS  - (7): e0200548
SP  - 1
EP  - 15
PB  - PLoS
CY  - Lawrence, Kan.
ER  -