Histomorphometric changes in repaired mouse sciatic nerves are unaffected by the application of a scar-reducing agent

Abstract

Microsurgical repair of transected peripheral nerves is compromised by the formation of scar tissue and the development of a neuroma, thereby limiting the success of regeneration. The aim of this study was to quantify histomorphometrically the structural changes in neural tissue that result from repair, and determine the effect of mannose-6-phosphate (M6P), a scar-reducing agent previously shown to enhance regeneration. In anaesthetised C57-black-6 mice, the left sciatic nerve was sectioned and repaired using four epineurial sutures. Either 100 lL of 600 mM M6P (five animals) or 100 lL of phosphate-buffered saline (placebo controls, five animals) was injected into and around the nerve repair site. A further group acted as sham-operated controls. After recovery for 6 weeks, the nerve was harvested for analysis using light and electron microscopy. Analysis revealed that when compared with sham controls, myelinated axons had smaller diameters both proximal and distal to the repair. Myelinated axon counts, axonal density and size all decreased across the repair site. There were normal numbers and densities of non-myelinated axons both proximal and distal to the repair. However, there were more Remak bundles distal to the repair site, and fewer non-myelinated axons per Remak bundle. Application of M6P did not affect any of these parameters.

The advances in nerve tissue engineering: From fabrication of nerve conduit toin vivonerve regeneration assays

“…After nerve damage, proliferation of fibroblasts around the nerve results in the formation of neuroma and subsequently forming a barrier to nerve ends at the site of nerve repair. However, these fibroblasts have also a mitogenic effect on SCs and eventually enhance remyelination in the nerve (Atkins et al, ; Dreesmann, Mittnacht, Lietz, & Schlosshauer, ; Ngeow et al, ; Wen & Zheng, ).…”

Assessment of the rate of spinal motor axon regeneration by choline acetyltransferase immunohistochemistry following sciatic nerve crush injury in mice

“…1,11,[16][17][18][19][20] This model is useful for testing the efficacy of new therapies for accelerating and enhancing axon growth and regeneration after injury. When compared with other models of peripheral nerve injury, sciatic nerve crush has several advantages, including easy access to the sciatic nerve.…”

The neurochemistry of peripheral nerve regeneration

“…Proliferation of fibroblasts in the epineurium, perineurium or endoneurium can result in scar that includes inhibitory proteoglycans (such as chondroitin sulphate) or semaphorins. [29,30] The scar forms mechanical barrier to the regenerating axons, causes shrinkage of the endoneurial sheaths that contain the axons and contributes to the development of multiple branched axonal terminals to form a neuroma. [31] The key for optimal nerve regeneration is to maintain or maximise the pro-regenerative capacity of the de-axonised distal nerve by ensuring the cell body and neuronal survival, to support recipient axonal regeneration (gap crossing and orientation of neuritis) to distal sensory/motor targets (NMJ and target muscle trophicity) as well as prevent neuroma (scar) formation.…”

“…Proliferation of fibroblasts in the epineurium, perineurium or endoneurium can result in scar that includes inhibitory proteoglycans (such as chondroitin sulphate) or semaphorins. [ 29 30 ] The scar forms mechanical barrier to the regenerating axons, causes shrinkage of the endoneurial sheaths that contain the axons and contributes to the development of multiple branched axonal terminals to form a neuroma. [ 31 ]…”