Evidence map›Paper›PMID 33499448›Full record

ArticleMilitary medicine2021

4-Aminopyridine: A Single-Dose Diagnostic Agent to Differentiate Axonal Continuity in Nerve Injuries.

Anagha A Gurjar, Kristen M Manto, Juan A Estrada, Marc Kaufman, Dongxiao Sun, M A Hassan Talukder, John C Elfar

Open access · bronzeAbstract read
In one paragraph

Article in Military medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.4field-weighted citation impact, top 48% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 4 citations in OpenAlex.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Anagha A GurjarDepartment of Orthopaedics and Rehabilitation, Center for Orthopaedics and Translational Science, The Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
Kristen M MantoDepartment of Orthopaedics and Rehabilitation, Center for Orthopaedics and Translational Science, The Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
Juan A EstradaHeart and Vascular Institute, The Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
Marc KaufmanHeart and Vascular Institute, The Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
Dongxiao SunMass Spectrometry Core Facility, Penn State University College of Medicine, Hershey, PA 17033, USA.
M A Hassan TalukderDepartment of Orthopaedics and Rehabilitation, Center for Orthopaedics and Translational Science, The Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
John C ElfarDepartment of Orthopaedics and Rehabilitation, Center for Orthopaedics and Translational Science, The Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
Pennsylvania State University · USCenter for Orthopaedics · USPenn State Milton S. Hershey Medical Center · US

Funding

Erythropoietin for NeuroregenerationK08AR060164 · NIAMS · UNIVERSITY OF ROCHESTER · PI ELFAR, JOHN · 2013 to 2017
$578k
NIAMS NIH HHS K08 AR060164
6 · The paper itself

Abstract

introductionTraumatic peripheral nerve injuries (TPNIs) are increasingly prevalent in battlefield trauma, and the functional recovery with TPNIs depends on axonal continuity. Although the physical examination is the main tool for clinical diagnosis with diagnostic work up, there is no diagnostic tool available to differentiate nerve injuries based on axonal continuity. Therefore, treatment often relies on "watchful waiting," and this leads to muscle weakness and further reduces the chances of functional recovery. 4-aminopyridine (4-AP) is clinically used in multiple sclerosis patients for walking performance improvement. Preliminary results in conscious mice suggested a diagnostic role of 4-AP in distinguishing axonal continuity. In this study, we thought to evaluate the diagnostic potential of 4-AP on the axonal continuity in unawake/sedated animals. MATERIALS AND

methodsRat sciatic nerve crush and transection injuries were used in this study. Briefly, rats were anesthetized with isoflurane and mechanically ventilated with oxygen-balanced vaporized isoflurane. Sciatic nerve and triceps surae muscles were exposed by blunt dissection, and a stimulating electrode was placed under a sciatic nerve proximal to the crush injury. A force transducer measured muscle tension response to electrical stimulation of sciatic nerve. Muscle response was measured before crush, after crush, and 30 minutes after systemic 4-AP (150 µg/kg) or local (4-AP)-poly(lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PLGA-PEG) treatment.

resultsWe found that both crush and transection injuries in sciatic nerve completely abolished muscle response to electrical stimulation. Single dose of systemic 4-AP and local (4-AP)-PLGA-PEG treatment with crush injury significantly restored muscle responses to electrical stimulation after 30 minutes of administration. However, systemic 4-AP treatment had no effect on muscle response after nerve transection. These results clearly demonstrate that 4-AP can restore nerve conduction and produce muscle response within minutes of administration only when there is a nerve continuity, even in the sedated animal.

conclusionsWe conclude that 4-AP could be a promising diagnostic agent in differentiating TPNI based on axonal continuity.

Indexed as

Axons4-AminopyridineAnimalsMaleMicePeripheral Nerve InjuriesRatsRats, Sprague-DawleyRecovery of FunctionSciatic Nerve4-Aminopyridine

Identifiers

PMID33499448
PMCPMC7832841
OpenAlexW3122397315

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.