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Functional recovery and muscle atrophy in pre-clinical models of peripheral nerve transection and gap-grafting in mice: effects of 4-aminopyridineopen access

Authors
Lee, Jung IlTalukder, M. A. HassanKaruman, ZaraGurjar, Anagha A.Govindappa, Prem KumarGuddadarangaiah, Jagadeeshaprasad M.Manto, Kristen M.Wandling, Grant D.Hegarty, John P.Waning, David L.Elfar, John C.
Issue Date
Feb-2023
Publisher
Neural Regeneration Research
Keywords
4-aminopyridine; functional recovery; muscle atrophy; nerve gap; nerve grafting; nerve imaging; nerve transection
Citation
Neural Regeneration Research, v.18, no.2, pp.439 - 444
Indexed
SCIE
SCOPUS
Journal Title
Neural Regeneration Research
Volume
18
Number
2
Start Page
439
End Page
444
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/61384
DOI
10.4103/1673-5374.346456
ISSN
1673-5374
Abstract
We recently demonstrated a repurposing beneficial effect of 4-aminopyridine (4-AP), a potassium channel blocker, on functional recovery and muscle atrophy after sciatic nerve crush injury in rodents. However, this effect of 4-AP is unknown in nerve transection, gap, and grafting models. To evaluate and compare the functional recovery, nerve morphology, and muscle atrophy, we used a novel stepwise nerve transection with gluing (STG), as well as 7-mm irreparable nerve gap (G-7/0) and 7-mm isografting in 5-mm gap (G-5/7) models in the absence and presence of 4-AP treatment. Following surgery, sciatic functional index was determined weekly to evaluate the direct in vivo global motor functional recovery. After 12 weeks, nerves were processed for whole-mount immunofluorescence imaging, and tibialis anterior muscles were harvested for wet weight and quantitative histomorphological analyses for muscle fiber cross-sectional area and minimal Feret's diameter. Average post-injury sciatic functional index values in STG and G-5/7 models were significantly greater than those in the G-7/0 model. 4-AP did not affect the sciatic functional index recovery in any model. Compared to STG, nerve imaging revealed more misdirected axons and distorted nerve architecture with isografting. While muscle weight, cross-sectional area, and minimal Feret's diameter were significantly smaller in G-7/0 model compared with STG and G-5/7, 4-AP treatment significantly increased right TA muscle mass, cross-sectional area, and minimal Feret's diameter in G-7/0 model. These findings demonstrate that functional recovery and muscle atrophy after peripheral nerve injury are directly related to the intervening nerve gap, and 4-AP exerts differential effects on functional recovery and muscle atrophy.
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Lee, Jung Il
구로병원 (Department of Orthopedic Surgery, Guro Hospital)
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