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

Autor:	Lee JI; Department of Orthopaedics and Rehabilitation, Center for Orthopaedic Research and Translational Science, The Pennsylvania State University College of Medicine, Hershey, PA, USA; Department of Orthopaedic Surgery, Korea University Guro Hospital, Seoul, South Korea., Talukder MAH; Department of Orthopaedics and Rehabilitation, Center for Orthopaedic Research and Translational Science, The Pennsylvania State University College of Medicine, Hershey, PA, USA., Karuman Z; Department of Orthopaedics and Rehabilitation, Center for Orthopaedic Research and Translational Science, The Pennsylvania State University College of Medicine, Hershey, PA, USA., Gurjar AA; Department of Orthopaedics and Rehabilitation, Center for Orthopaedic Research and Translational Science, The Pennsylvania State University College of Medicine, Hershey, PA, USA., Govindappa PK; Department of Orthopaedics and Rehabilitation, Center for Orthopaedic Research and Translational Science, The Pennsylvania State University College of Medicine, Hershey, PA, USA., Guddadarangaiah JM; Department of Orthopaedics and Rehabilitation, Center for Orthopaedic Research and Translational Science, The Pennsylvania State University College of Medicine, Hershey, PA, USA., Manto KM; Department of Orthopaedics and Rehabilitation, Center for Orthopaedic Research and Translational Science, The Pennsylvania State University College of Medicine, Hershey, PA, USA., Wandling GD; Department of Orthopaedics and Rehabilitation, Center for Orthopaedic Research and Translational Science, The Pennsylvania State University College of Medicine, Hershey, PA, USA., Hegarty JP; Department of Orthopaedics and Rehabilitation, Center for Orthopaedic Research and Translational Science, The Pennsylvania State University College of Medicine, Hershey, PA, USA., Waning DL; Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA, USA., Elfar JC; Department of Orthopaedics and Rehabilitation, Center for Orthopaedic Research and Translational Science, The Pennsylvania State University College of Medicine, Hershey, PA, USA.
Jazyk:	angličtina
Zdroj:	Neural regeneration research [Neural Regen Res] 2023 Feb; Vol. 18 (2), pp. 439-444.
DOI:	10.4103/1673-5374.346456
Abstrakt:	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. Competing Interests: None
Databáze:	MEDLINE
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