Sensory Neuron Death After Upper Limb Nerve Injury and Protective Effect of Repair

West, Christian A; Ljungberg, Christina; Wiberg, Mikael; Hart, Andrew

doi:10.1227/neu.0000000000000066

Cited by 13 publications

(8 citation statements)

References 34 publications

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“…In this study, we demonstrated that our in vitro culture system may provide a suitable model to investigate peripheral sensory neuronal cell death. Previous experimental studies have indicated that peripheral nerve axotomy induces DRG sensory neuron death and this observation is supported indirectly by our previous clinical studies showing significant loss of DRG volume in nerve-injured patients 46 . Oxidative stress has been suggested to be a mediator of this cell death since anti-oxidants such as N-acetyl cysteine (NAC) are neuroprotective 33 .…”

Section: Discussionsupporting

confidence: 59%

Development and validation of an in vitro model system to study peripheral sensory neuron development and injury

Jones

Yelhekar

Wiberg

et al. 2018

Sci Rep

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The ability to discriminate between diverse types of sensation is mediated by heterogeneous populations of peripheral sensory neurons. Human peripheral sensory neurons are inaccessible for research and efforts to study their development and disease have been hampered by the availability of relevant model systems. The in vitro differentiation of peripheral sensory neurons from human embryonic stem cells therefore provides an attractive alternative since an unlimited source of biological material can be generated for studies that specifically address development and injury. The work presented in this study describes the derivation of peripheral sensory neurons from human embryonic stem cells using small molecule inhibitors. The differentiated neurons express canonical- and modality-specific peripheral sensory neuron markers with subsets exhibiting functional properties of human nociceptive neurons that include tetrodotoxin-resistant sodium currents and repetitive action potentials. Moreover, the derived cells associate with human donor Schwann cells and can be used as a model system to investigate the molecular mechanisms underlying neuronal death following peripheral nerve injury. The quick and efficient derivation of genetically diverse peripheral sensory neurons from human embryonic stem cells offers unlimited access to these specialised cell types and provides an invaluable in vitro model system for future studies.

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Section: Discussionsupporting

confidence: 59%

Development and validation of an in vitro model system to study peripheral sensory neuron development and injury

Jones

Yelhekar

Wiberg

et al. 2018

Sci Rep

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“…Also in the context of degenerative or traumatic processes, the imaging observation of DRG vol seems valuable because it correlates strongly with the number of DRG sensory neurons, allowing conclusions about local neurodegeneration and loss of neurons. 18 For example, changes in the quantity of neurons could be observed in experimental diabetes models with a loss of large DRG neurons that, on a functional level, was associated with slowed sensory 6, including an intercept, only slightly overestimating voxelwise ground truth segmentation. The pink shell just at the inside of the green shell corresponds to the new and second-best-performing Equation 5, without an intercept, slightly underestimating DRG vol (r).…”

Section: Discussionmentioning

confidence: 99%

Dorsal Root Ganglion Volumetry by MR Gangliography

Weiner¹,

Strinitz²,

Herfurth³

et al. 2022

AJNR Am J Neuroradiol

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BACKGROUND AND PURPOSE: Dorsal root ganglion MR imaging (MR gangliography) is increasingly gaining clinical-scientific relevance. However, dorsal root ganglion morphometry by MR imaging is typically performed under the assumption of ellipsoid geometry, which remains to be validated. MATERIALS AND METHODS:Sixty-four healthy volunteers (37 [57.8%] men; mean age, 31.5 [SD, 8.3] years) underwent MR gangliography of the bilateral L4-S2 levels (3D-T2WI TSE spectral attenuated inversion recovery-sampling perfection with application-optimized contrasts by using different flip angle evolution, isotropic voxels = 1.1 mm 3 , TE = 301 ms). Ground truth dorsal root ganglion volumes were bilaterally determined for 96 dorsal root ganglia (derivation cohort) by expert manual 3D segmentation by 3 independent raters. These ground truth dorsal root ganglion volumes were then compared with geometric ellipsoid dorsal root ganglion approximations as commonly practiced for dorsal root ganglion morphometry. On the basis of the deviations from ellipsoid geometry, improved volume estimation could be derived and was finally applied to a large human validation cohort (510 dorsal root ganglia). RESULTS:Commonly used equations of ellipsoid geometry underestimate true dorsal root ganglion volume by large degrees (factor = 0.42-0.63). Ground truth segmentation enabled substantially optimizing dorsal root ganglion geometric approximation using its principal axes lengths by deriving the dorsal root ganglion volume term of 2 3 Â A Â B Â C þ 75 mm 3 . Using this optimization, the mean volumes of 510 lumbosacral healthy dorsal root ganglia were as follows: L4: 211.3 (SD, 52.5) mm 3 , L5: 290.7 (SD, 90.9) mm 3 , S1: 384.2 (SD, 145.0) mm 3 , and S2: 192.4 (SD, 52.6) mm 3 . Dorsal root ganglion volume increased from L4 to S1 and decreased from S1 to S2 (P , .001). Dorsal root ganglion volume correlated with subject height (r = . 22, P , .001) and was higher in men (P , .001).CONCLUSIONS: Dorsal root ganglion volumetry by measuring its principal geometric axes on MR gangliography can be substantially optimized. By means of this optimization, dorsal root ganglion volume distribution was estimated in a large healthy cohort for the clinically most relevant lumbosacral levels, L4-S2.

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“…Similar time-dependent effects are seen in the nerve—a decline in Schwann cell number and an increase in fibrosis and scarring in the distal nerve stump 27 . Central cell death in the dorsal root ganglion and anterior horn cells is also time-dependent and can be limited by early nerve repair 28,29 . Animal and human studies report 3 months to be the critical point after which recovery is destined to be poor 27,30 .…”

Section: Discussionmentioning

confidence: 81%

Median Nerve Palsy in Pediatric Supracondylar Humerus Fractures Recovers Faster With Open Than Closed Reduction

Wilks,

Ye,

Biggins

et al. 2023

Journal of Pediatric Orthopaedics

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Background: Management of supracondylar humerus fractures (SCHF) with coexisting median nerve injury is controversial. Although many nerve injuries improve with the reduction and stabilization of the fracture, the speed and completeness of recovery are unclear. This study investigates median nerve recovery time using the serial examination. Methods: A prospectively maintained database of SCHF-related nerve injuries referred to a tertiary hand therapy unit between 2017 and 2021 was interrogated. Factors related to the injury (vascularity, Gartland grade, open vs. closed fracture) and treatment (fixation modality, adequacy, timing of reduction, vascular and nerve intervention, and secondary procedures) were assessed. Primary outcomes were the motor recovery of Medical Research Council (MRC) grade 4 or 5 in flexor pollicis longus or flexor digitorum profundus (index) and detection of the 2.83 Semmes Weinstein monofilament. A retrospective clinical note review of all SCHF presenting during the same period was also conducted. Results: Of 1096 SCHF, 74 (7%) had an associated median nerve palsy. Twenty-one patients [mean age 7 years (SD 1.6)] with SCHF-related median nerve injuries underwent serial examination. Nineteen (90%) were modified Gartland III or IV, and 10 (48%) were pulseless on presentation. The mean follow-up was 324 days. The mean motor recovery time was 120 days (SD 71). Four (27%) and 2 (13%) patients had not achieved MRC grade 4 by 6 months and 2 years, respectively. Only 50% attained MRC grade 5 at 2 years. When compared with closed reduction, those who underwent open reduction recovered motor function 80 days faster (mean 71 vs. 151 d, P=0.03) and sensory function 110 days faster (52 vs. 162, P=0.02). Fewer patients recovered after closed reduction (8 of 10) than open (5 of 5). Modified Gartland grade, vascular status, adequacy of reduction, and secondary surgery were not associated with recovery time. Conclusions: Median nerve recovery seems to occur slower than previously thought, is often incomplete, and is affected by treatment decisions (open vs. closed reduction). Retrospective reporting methods may overestimate median nerve recovery. Level of Evidence: Level III—therapeutic.

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Sensory Neuron Death After Upper Limb Nerve Injury and Protective Effect of Repair

Cited by 13 publications

References 34 publications

Development and validation of an in vitro model system to study peripheral sensory neuron development and injury

Development and validation of an in vitro model system to study peripheral sensory neuron development and injury

Dorsal Root Ganglion Volumetry by MR Gangliography

Median Nerve Palsy in Pediatric Supracondylar Humerus Fractures Recovers Faster With Open Than Closed Reduction

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