Salomone et al did not induce PEG‐fusion repair of severed rat facial nerves

Bittner, George D.; Ghergherehchi, Cameron L.; Mikesh, Michelle; Sengelaub, Dale R.; Trevino, Richard; Shores, Jaimie T.

doi:10.1002/hed.25894

Cited by 1 publication

(4 citation statements)

References 16 publications

(67 reference statements)

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“…PNAs (Figure 3a,b). If these initial recordings are not made, initial PEG-fusion may be unsuccessful but is not recognized, invalidating the data of those individual nerves as an example of "successful PEGfusion" (Bittner et al, 2019;.…”

Section: Summary Of Resultsmentioning

confidence: 99%

“…Our results for CAPS and CMAPs taken before, during, and immediately after our PEG‐fusion procedure provide strong electrophysiological evidence that axonal continuity across the graft is rapidly restored in PEG‐fused PNAs, but not in negative control PNAs (Figure 3a,b). If these initial recordings are not made, initial PEG‐fusion may be unsuccessful but is not recognized, invalidating the data of those individual nerves as an example of “successful PEG‐fusion” (Bittner et al., 2019; Ghergherehchi, Mikesh, et al., 2019). This error almost certainly occurred in several recently reported studies of putative PEG‐fusion (Brown et al., 2019; Robinson & Madison, 2016; Solomone et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…As assessed by the SFI after ablation‐type PNIs to rat sciatic nerves, PEG‐fusion does not significantly ( p < 0.05) restore voluntary walking behaviors at 42 days PO in about 5% of cases for well‐trained graduate or undergraduate surgeons. PEG‐fusion success can be 0% for other undergraduates, graduates, faculty, or clinicians who are not well trained or do not follow published PEG‐fusion protocols (Bittner et al., 2017, 2019; Ghergherehchi, Mikesh, et al., 2019).…”

Section: Methodsmentioning

confidence: 99%

“…Animals were first tested 3 days after surgery, then weekly for up to 42 days PO. Criteria for successful SFI assessments required that: animals must run for three consecutive hind limb steps without hesitating or stopping (Varejao, Meek, Ferreira, Patricio, & Cabrita, 2001 (Bittner et al, 2017(Bittner et al, , 2019. Medinaceli, 1995).…”

Section: Behavioral Analysesmentioning

confidence: 99%

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Polyethylene glycol‐fusion repair of sciatic allografts in female rats achieves immunotolerance via attenuated innate and adaptive responses

Smith

Ghergherehchi

Mikesh

et al. 2020

J of Neuroscience Research

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Ablation/segmental loss peripheral nerve injuries (PNIs) exhibit poor functional recovery due to slow and inaccurate outgrowth of regenerating axons. Viable peripheral nerve allografts (PNAs) as growth-guide conduits are immunologically rejected and all anucleated donor/host axonal segments undergo Wallerian degeneration. In contrast, we report that ablation-type sciatic PNIs repaired by neurorrhaphy of viable sciatic PNAs and a polyethylene glycol (PEG)-fusion protocol using PEG immediately restored axonal continuity for many axons, reinnervated/maintained their neuromuscular junctions, and prevented much Wallerian degeneration. PEG-fused PNAs permanently restored many sciatic-mediated behaviors within 2-6 weeks. PEG-fused PNAs were not rejected even though host/donors were neither immunosuppressed nor tissue-matched in outbred female Sprague Dawley rats. Innate and adaptive immune responses to PEG-fused sciatic PNAs were analyzed using electron microscopy, immunohistochemistry, and quantitative reverse transcription polymerase chain reaction for morphological features, T cell and macrophage infiltration, major histocompatibility complex (MHC) expression, apoptosis, expression of cytokines, chemokines, and cytotoxic effectors. PEG-fused PNAs exhibited attenuated innate and adaptive immune responses by 14-21 days postoperatively, as evidenced by (a) many axons and cells remaining viable, (b) significantly reduced infiltration of cytotoxic and total T cells and macrophages, (c) significantly reduced expression of inflammatory cytokines, chemokines, and MHC proteins, (d) consistently low apoptotic response. Morphologically and/or biochemically, PEG-fused sciatic PNAs often resembled sciatic autografts or intact sciatic nerves. In brief, PEG-fused PNAs are an unstudied, perhaps unique, example of immune tolerance of viable allograft tissue in a nonimmune-privileged environment and could greatly improve the clinical outcomes for PNIs relative to current protocols.

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Section: Summary Of Resultsmentioning

confidence: 99%