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Surgery for nerve injury: current and future perspectives

JNSPG 75th Anniversary Invited Review Article

Rajiv Midha and Joey Grochmal

In Brief

The authors conducted a brief historical review of nerve repair methods over the past 100 years, with a more detailed review and account on how the advent of nerve transfer procedures in the past 2 decades are improving outcomes in patients with nerve injuries. The paper offers the authors' expert perspective on contemporary practice of nerve surgery for nerve injury repair, in addition to recent exciting innovations and evolution in surgical management.

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Joey Grochmal, Wulin Teo, Hardeep Gambhir, Ranjan Kumar, Jo Anne Stratton, Raveena Dhaliwal, Craig Brideau, Jeff Biernaskie, Peter K. Stys and Rajiv Midha

OBJECTIVE

Intravital spectral imaging of the large, deeply situated nerves in the rat peripheral nervous system (PNS) has not been well described. Here, the authors have developed a highly stable platform for performing imaging of the tibial nerve in live rodents, thus allowing the capture of high-resolution, high-magnification spectral images requiring long acquisition times. By further exploiting the qualities of the topically applied myelin dye Nile red, this technique is capable of visualizing the detailed microenvironment of peripheral nerve demyelination injury and recovery, while allowing us to obtain images of exogenous Schwann cell myelination in a living animal.

METHODS

The authors caused doxorubicin-induced focal demyelination in the tibial nerves of 25 Thy-1 GFP rats, of which 2 subsets (n = 10 each) received either BFP-labeled SKP-SCs or SCs to the zone of injury. Prior to acquiring images of myelin recovery in these nerves, a tibial nerve window was constructed using a silicone hemitube, a fast drying silicone polymer, and a small coverslip. This construct was then affixed to a 3D-printed nerve stage, which in turn was affixed to an external fixation/microscope stage device. Myelin visualization was facilitated by the topical application of Nile red.

RESULTS

The authors reliably demonstrated intravital peripheral nerve myelin imaging with micron-level resolution and magnification, and minimal movement artifact. The detailed microenvironment of nerve remyelination can be vividly observed, while exogenously applied Schwann cells and skin-derived precursor Schwann cells can be seen myelinating axons.

CONCLUSIONS

Topically applied Nile red enables intravital study of myelin in the living rat PNS. Furthermore, the use of a tibial nerve window facilitates stable intravital peripheral nerve imaging, making possible high-definition spectral imaging with long acquisition times.