The endoneurial response to microsurgically removed epi‐ and perineurium

Abstract

The purpose of the study was to examine the response of the endoneurium of the rat sciatic nerve after removal of the epi- and perineurium. For this purpose, segments (4-5 mm long) of the whole epi- and perineurium around the rat sciatic nerve were microsurgically removed (the peel-off area) and the endoneurium was left intact. The post-operative changes were followed up to 5 weeks post-operatively (PO) by histo- and immunohistochemical studies. Additionally, neuromorphometric analyses considering the number of Schwann cells, axons, macrophages and endothelial cells were examined in the peel-off area. The results showed that at the operative area the central part of the endoneurium (65% of the total area of the endoneurium) remained morphologically intact, but the outer part of the endoneurium (35% of the total area) reacted strongly and showed Wallerian type of degeneration. The number of axons and Schwann cells decreased 3 days PO. However, after 2 weeks the number of Schwann cells increased markedly and the highest number was noted 5 weeks PO. A great number of capillaries were observed in the outer part 1 week PO. A rapid invasion of macrophages was noted at the outer part of the endoneurium immediately after the operation. During the regeneration the endoneurial fibroblasts in the peripheral zone started to form minifascicle-like formations, which resulted in a distinct dense outer part of the endoneurium. This dense outer zone was preserved up to 5 weeks PO and participated in the formation of a new perineurium-like structure, but no distinct new perineurium was formed. At the border zone, areas beside the normal epi- and perineurium proliferation of preserved perineurial cells were noted, which fused to the outer part of the dense endoneurium. On focal areas, an attachment of the operated area to the adjoining muscle was observed. This study shows for the first time that despite the microsurgical removal of epi- and perineurium, the inner part of the endoneurium stays intact, but in the outer part of the endoneurium marked reactive changes ensue, probably to protect the injured peripheral nerve.

Novel Polysaccharide‐derived hydrogel prevents perineural adhesions in a rat model of sciatic nerve adhesion

“…This procedure is a method of extensive internal neurolysis 11. Terho et al22 investigated endoneurial responses to microsurgically removed epi‐ and perineurium of the rat sciatic nerve for a length of 4 to 5 mm and found the endoneurium adhered to adjoining muscle. We used this model as a sciatic nerve adhesion model.…”

Desert hedgehog-patched 2 expression in peripheral nerves during Wallerian degeneration and regeneration

“…Minifascicular formation in peripheral nerves has been reported in injury models when the perineurium is destroyed or resected (Popovic et al, 1994;Terho et al, 2002). Similarly, vulnerability of the perineurium in the PNS of dhh-null mice may result in extensive minifascicular formation after injury.…”

Influence of Breaching the Connective Sheaths of the Donor Nerve on Its Myelinated Sensory Axons and on Their Sprouting into the End-to-Side Coapted Nerve in the Rat

“…It is interesting in this regard, that during 5 weeks after the stripping of the perineurium, a new sheath, closely resembling normal perineurium, became organized throughout the length of the injured nerve segment. 45,68 Taken together, these results suggest that in order to enhance axon sprouting from the donor nerve into the recipient one, the primary injury of the epineurium, not the perineurium, is critical. Second, by increasing the degree of breach in the donor nerve connective tissue sheaths (ranging from the epineurial sutures to the perineurial window), axon sprouting into the recipient nerve is accelerated, but its final magnitude is not significantly affected.…”

“…Namely, subepineurial demyelination, degeneration, and axonal sprouting were found also after stripping the vessels from the epineurium, as well as after perineurial windowing or in experimental entrapment neuropathies with chronic loose ligatures. 42,45,67 However, once the axon sprouting from the donor nerve is enhanced, the ingrowth of sprouting axons into the recipient nerve depends upon the soluble and insoluble factors provided by the Schwann cells from the recipient nerve. 47,60 Therefore, it is possible that even the small holes created by needle penetration and sutures through the epineurium during the end-to-side repair are sufficient to enhance growth factor diffusion or Schwann cell migration in the early postoperative period.…”

“…On the other hand, surgical breaching of the epineurium and perineurium may result in a marked axonal injury in the peripheral regions of the endoneurium. [42][43][44][45] As one would wish to maximize the ingrowth of axons into the recipient nerve with concomitantly causing as little injury to the donor nerve as possible, the question 1 of whether an epineurial or even perineurial window should be created at the site of nerve coaptation became an important issue regarding the end-to-side nerve repair.…”