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 Il; Talukder, M. A. Hassan; Karuman, Zara; Gurjar, Anagha A.; Govindappa, Prem Kumar; Guddadarangaiah, 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
- Pages
- 6
- 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
1876-7958
- 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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- Appears in
Collections - 2. Clinical Science > Department of Orthopedic Surgery > 1. Journal Articles
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