Neurofilament-histomorphometry comparison in the evaluation of unmyelinated axon regeneration following peripheral nerve injury: An alternative to electron microscopy

Hendry, Joy; Alvarez-Veronesi, M. Cecilia; Chiang, Cameron; Gordon, Tessa; Borschel, Gregory H.

doi:10.1016/j.jneumeth.2019.03.006

Cited by 9 publications

(8 citation statements)

References 23 publications

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“…Because the CNAP is a population response aggregate from the action potentials generated by every individual axon in the mixed median nerve, including all sizes and all functional axon types, one explanation for this finding could be the unequal rate of remyelination for different subgroups of regenerating axons, likely determined by axon diameter and functional classification. Therefore, as different subpopulations of axons regenerate at different rates, each subgroup will conduct along the gap at differing mean NCVs such that the resulting CNAP has multiple waveform components across a broad range of peak latencies, and various proportions of axons in each group remain unmyelinated after peripheral nerve injury (63). This robust finding of multipeaked CNAP waveforms only for autograft CNAPs suggests that the remyelination process for autografts was delayed in contrast to a more complete remyelination for PCL/GDNF conduits.…”

Section: Discussionmentioning

confidence: 99%

Long-gap peripheral nerve repair through sustained release of a neurotrophic factor in nonhuman primates

et al. 2020

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Severe injuries to peripheral nerves are challenging to repair. Standard-of-care treatment for nerve gaps >2 to 3 centimeters is autografting; however, autografting can result in neuroma formation, loss of sensory function at the donor site, and increased operative time. To address the need for a synthetic nerve conduit to treat large nerve gaps, we investigated a biodegradable poly(caprolactone) (PCL) conduit with embedded double-walled polymeric microspheres encapsulating glial cell line–derived neurotrophic factor (GDNF) capable of providing a sustained release of GDNF for >50 days in a 5-centimeter nerve defect in a rhesus macaque model. The GDNF-eluting conduit (PCL/GDNF) was compared to a median nerve autograft and a PCL conduit containing empty microspheres (PCL/Empty). Functional testing demonstrated similar functional recovery between the PCL/GDNF-treated group (75.64 ± 10.28%) and the autograft-treated group (77.49 ± 19.28%); both groups were statistically improved compared to PCL/Empty-treated group (44.95 ± 26.94%). Nerve conduction velocity 1 year after surgery was increased in the PCL/GDNF-treated macaques (31.41 ± 15.34 meters/second) compared to autograft (25.45 ± 3.96 meters/second) and PCL/Empty (12.60 ± 3.89 meters/second) treatment. Histological analyses included assessment of Schwann cell presence, myelination of axons, nerve fiber density, and g-ratio. PCL/GDNF group exhibited a statistically greater average area occupied by individual Schwann cells at the distal nerve (11.60 ± 33.01 μm2) compared to autograft (4.62 ± 3.99 μm2) and PCL/Empty (4.52 ± 5.16 μm2) treatment groups. This study demonstrates the efficacious bridging of a long peripheral nerve gap in a nonhuman primate model using an acellular, biodegradable nerve conduit.

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Section: Discussionmentioning

confidence: 99%

Long-gap peripheral nerve repair through sustained release of a neurotrophic factor in nonhuman primates

et al. 2020

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“…Choline acetyltransferase is specific for neurotransmitter enzymes found in cholinergic axons, axon terminals, cell bodies, and dendrites of motor and parasympathetic autonomic fibers 15,17,18,20 . Neurofilament 1 has proven to be useful for counting total axons within a nerve fiber 19–21 . By calculating the difference between ChAT- and NF-1–stained axon counts, we estimated the total sensory axons in a given nerve specimen.…”

Section: Discussionmentioning

confidence: 99%

“…15,17,18,20 Neurofilament 1 has proven to be useful for counting total axons within a nerve fiber. [19][20][21] By calculating the difference between ChAT-and NF-1-stained axon counts, we estimated the total sensory axons in a given nerve specimen. Interestingly, some studies have identified ChAT uptake in sensory mechanoreceptors pathways, and it is possible that our ChAT staining may have unintentionally stained mixed areas of sensory and motor axons.…”

Section: Discussionmentioning

confidence: 99%

“…Immunohistochemical studies have demonstrated antibodies directed against ChAT stain cholinergic fibers, including motor and parasympathetic efferent fibers 15–18 . Neurofilament 1 stains all axonal fibers with neurofilaments, a major component of the neural scaffold 19–21 …”

Section: Methodsmentioning

confidence: 99%

“…[15][16][17][18] Neurofilament 1 stains all axonal fibers with neurofilaments, a major component of the neural scaffold. [19][20][21] Formalin-fixed paraffin-embedded tissues were sectioned at 5 μm, placed on slides and warmed overnight at 60°C. Slides were deparaffinized and rehydrated with graded alcohols ending in Tris buffered saline (TBS-T Wash Buffer; LabVision, Freemont, Calif ).…”

Section: Laboratory Examinationmentioning

confidence: 99%

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Anatomic Comparison of Recipient Nerves for Deep Inferior Epigastric Perforator Flap Neurotization

et al. 2022

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IntroductionAlthough neurotization has the potential to improve sensory outcomes after autologous breast reconstruction, this technique remains controversial. There is debate regarding the clinical outcomes and the recipient nerve of choice. This histoanatomical study aims to quantitatively compare the sensory components of the recipient nerves involved in neurotization of the deep inferior epigastric perforator flap.MethodsSubjects undergoing bilateral autologous breast reconstruction were enrolled. Transected nerve specimens underwent immunohistochemical staining with antibodies against neurofilament 1 and choline acetyltransferase for total and motor neurons within the axons, respectively. Photomicrographs were captured, and axons were analyzed using ImageJ. Sensory axons were calculated as equal to the difference between the total and cholinergic axonal counts.ResultsThirty-eight nerves from 19 subjects were included. The overall mean sensory axon count was 1246.3 (±1171.9) in the lateral cutaneous branch (LCB) of the fourth intercostal nerve and 1123.8 (±1213.0) in the anterior cutaneous branch (ACB) of the third intercostal nerve.The fourth LCB presented with an additional 10.9% sensory axonal count (P > 0.05). On average, sensory fibers constituted 36.7% and 31.7% of all fibers in the third ACBs and fourth LCBs, respectively.ConclusionsThis study provides anatomic and histological evidence that the fourth LCB and third ACB contain comparable mean numbers of sensory axons. Both constitute adequate recipient nerves for coaptation in deep inferior epigastric perforator reinnervation to achieve optimal sensory return after breast reconstruction. The fourth LCB should be preferable when the third ACB remains intact to preserve any native breast flap sensation.

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Combination of stem cells and nerve guide conduit for the treatment of peripheral nerve injury: A meta‐analysis

Cao,

Yihao,

et al. 2023

Muscle and Nerve

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Introduction/AimsMany small‐sized, single‐center preclinical studies have investigated the benefits of introducing stem cells into the interior of nerve conduit. The aims of this meta‐analysis are to review and contrast the effects of various types of stem cells in in vivo models used to reconstruct peripheral nerve injuries (PNIs) and to assess the reliability and stability of the available evidence.MethodsA systematic search was conducted using Cochrane Library, Embase, PubMed, and Web of Science to identify studies conducted from January 1, 2000, to September 21, 2022, and investigate stem cell therapy in peripheral nerve reconstruction animal models. Studies that met the relevant criteria were deemed eligible for this meta‐analysis.ResultsFifty‐five preclinical studies with a total of 1234 animals were incorporated. Stem cells demonstrated a positive impact on peripheral nerve regeneration at different follow‐up times in the forest plots of five outcome indicators: compound muscle action potential (CMAP) amplitude, latency, muscle mass ratio, nerve conduction velocity, and sciatic functional index (SFI). In most comparisons, stem cell groups showed substantial differences compared with the control groups. The superior performance of adipose‐derived stem cells (ADSCs) in terms of SFI, CMAP amplitude, and latency (p < .001) was identified.DiscussionThe findings consistently demonstrated a favorable outcome in the reconstruction process when utilizing different groups of stem cells, as opposed to control groups where stem cells were not employed.

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Neurofilament-histomorphometry comparison in the evaluation of unmyelinated axon regeneration following peripheral nerve injury: An alternative to electron microscopy

Cited by 9 publications

References 23 publications

Long-gap peripheral nerve repair through sustained release of a neurotrophic factor in nonhuman primates

Long-gap peripheral nerve repair through sustained release of a neurotrophic factor in nonhuman primates

Anatomic Comparison of Recipient Nerves for Deep Inferior Epigastric Perforator Flap Neurotization

Combination of stem cells and nerve guide conduit for the treatment of peripheral nerve injury: A meta‐analysis

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