Biology subjects

Midha, R.

Publications and source records attributed to Midha, R..

2 recordsLinked to original sources

bioRxiv2025

Inferior Reinnervation of Reverse End-to-Side Nerve Transfer in a Delayed Nerve Repair Rat Model

ObjectiveReverse end-to-side (RETS) nerve transfer is a recent surgical technique to augment injured nerve function by supplying a dispensable donor motor nerve to the side of the distal injured nerve. Although clinical studies have suggested advantages of RETS transfer for upper extremity repairs, uncertainties remain regarding its underlying mechanism. Furthermore, our recent clinical studies using electrophysiological examinations revealed no contribution from the donor nerve. Given that most experimental studies were conducted on acutely injured nerves, our objective is to 1) reassess the effectiveness RETS nerve transfer in a rat model of chronic nerve injury and repair; 2) investigate the potential nerve-babysitting effect; and 3) investigate how availability of regenerating tracks, i.e. bands of Bungner, of recipient nerve affects donor nerve regeneration. MethodsObturator and femoral nerve were used as donor and recipient nerves, respectively. Electromyogram, retrograde labeling of regenerated motoneurons and neuromuscular junction (NMJ) formation were used to compare regenerative ability of donor nerve in acute and delayed RETS transfer where the femoral nerve in the latter group was injured by double ligations 8 weeks prior. Nerve-babysitting effect on injured nerve was investigated by 1) no intervention; 2) perineurial window creation; and 3) RETS transfer to femoral nerve in delayed repair model. The effects of availability of regeneration tracks were investigated by severing proximal femoral nerve, allowing complete denervation compared partial denervation in double ligations, followed by acute and delayed repairs. ResultsEMG and motoneuron quantification confirmed inferiority of donor nerve regeneration into recipient nerve in delayed RETS transfer compared to acute repair, yet donor axons reached target muscle and formed NMJs in both conditions. Same functional assessments revealed nerve baby-sitting effects did not significantly contribute to repair success but availability of regeneration tracks in the recipient nerve may influence the final outcomes. ConclusionsOur study offered insights into the effectiveness of RETS nerve transfer in clinically relevant settings, underscoring the compounded impact of delayed intervention and native nerve regeneration which both negatively affect the efficacy of RETS nerve transfer.

neuroscience↗

bioRxiv2020

Etv5 is not required for Schwann cell development but is required to regulate the Schwann cell response to peripheral nerve injury

Schwann cells are the principal glial cells of the peripheral nervous system, and their development into myelinating glia is critically dependent on MEK/ERK signaling. Ets-domain transcription factors (Etv1, Etv4, Etv5) are common downstream effectors of MEK/ERK signalling, but so far, only Etv1 has been ascribed a role in Schwann cell development, and only in non-myelinating cells. Here, we examined the role of Etv5, which is expressed in Schwann cell precursors, including neural crest cells and satellite glia, in Schwann cell lineage development. We analysed Etv5tm1Kmm mutants (designated Etv5-/-) at embryonic days (E) 12.5, E15.5 and E18.5, focusing on dorsal root ganglia. At these embryonic stages, satellite glia (glutamine synthetase) and Schwann cell markers, including transcriptional regulators (Sox10, Sox9, Tfap2a, Pou3f1) and non-transcription factors (Ngfr, BFABP, GFAP), were expressed in the DRG of wild-type and Etv5-/- embryos. Furthermore, by E18.5, quantification of Sox10+ Schwann cells and NeuN+ neurons revealed that these cells were present in normal numbers in the Etv5-/- dorsal root ganglia. We next performed peripheral nerve injuries at postnatal day 21, revealing that Etv5-/- mice had an enhanced injury response, generating more Sox10+ Schwann cells compared to wild-type animals at five days post-injury. Thus, while Etv5 is not required for Schwann cell development, possibly due to genetic redundancy with Etv1 and/or Etv4, Etv5 is an essential negative regulator of the peripheral nerve injury repair response. SIGNIFICANCE STATEMENTOur study sought to determine whether the ets domain transcription factor, Etv5, plays a role in regulating Schwann cell development and nerve repair. By using an embryonically and postnatally viable hypomorphic Etv5 mutant allele, we demonstrated that Etv5 is not required for the development of Schwann cells or other neural crest derivatives in the dorsal root ganglia, including satellite glia and neurons. Surprisingly, loss of Etv5 had a direct impact on the Schwann cell repair response post-injury, resulting in more Schwann cells populating the distal injured nerve site compared to wild-type animals. Thus, this work describes for the first time a role for Etv5 in regulating the Schwann cell repair response after peripheral nerve injury.

developmental biology↗