Denatured muscle grafts for nerve repair in an experimental model of nerve damage in leprosy. 2. Recovery of peripheral peptide-containing nerves assessed by quantitative immunohistochemical study.
A marked depletion of neuropeptide-immunoreactive nerves, a consequence of the nerve damage which is commonly found in leprosy, has been reported in peripheral tissues of leprosy patients and of a leprosy animal model. The aim of this study was to investigate peripheral reinnervation following a denatured autologous muscle graft in an animal model of leprosy nerve damage. Possible reinnervation of the foot-pad skin was studied by immunohistochemistry using antisera to the neuronal marker protein gene product 9.5 (PGP), the neuropeptides calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP), and the C-flanking peptide of neuropeptide Y (CPON). The extent of the reinnervation process was assessed by image analysis quantification at different time points. At 8 weeks after muscle grafting, there were small numbers of immunoreactive nerves (p < 0.05). At 12, 16, and 20 weeks postoperatively there was a gradual increase in all immunostaining. At 20 weeks, no significant difference was found for PGP-, CGRP-, and SP-immunoreactive nerves in the epidermal and subepidermal layers compared to control (contralateral) tissue. In experimental tissue the recovery of immunoreactive nerves around sweat glands took longer (up to 12 weeks) than in other skin compartments, but after that time the recovery was rapid and at 20 weeks no difference was measured for VIP-immunoreactive nerves in comparison with controls. Around blood vessels, the recovery of CGRP- and CPON-immunoreactive fibers was slow, and at 20 weeks a difference with control samples (p < 0.01) was noted. In the same area, there was no significant difference for PGP immunoreactivity between controls and tissues at 20 weeks. In contrast, the immunoreactive nerve bundles in the dermis showed a faster recovery than nerves in other skin areas, with amounts similar to controls at 20 weeks. The significant recovery of immunoreactive nerves, in particular of those containing sensory neuropeptide, is consistent with the described functional recovery.
Santamaria
L
L
Department of Histochemistry, Royal Postgraduate Medical School, Hammersmith Hospital, London, U.K.
Terenghi
G
G
Curtis
J
J
de Blaquière
G E
GE
Pereira
J H
JH
Turk
J L
JL
Polak
J M
JM
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis; D006099:Granuloma / Q000378:metabolism / Q000601:surgery*; D006168:Guinea Pigs; D007150:Immunohistochemistry; D007918:Leprosy / Q000150:complications*; D009132:Muscles / Q000637:transplantation*; D009479:Neuropeptides / Q000032:analysis*; D010523:Peripheral Nervous System Diseases / Q000378:metabolism / Q000601:surgery*; D013373:Substance P / Q000032:analysis; D013869:Thiolester Hydrolases / Q000032:analysis; D043222:Ubiquitin Thiolesterase
D009479:Neuropeptides; D013373:Substance P; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase; D015740:Calcitonin Gene-Related Peptide