Reinnervation and neuropeptides in mouse skin flaps

Karanth, Subramanya; Dhital, Sanjiv K.; Springall, David R.; Polak, Julia M.

doi:10.1016/0165-1838(90)90069-u

Cited by 48 publications

(22 citation statements)

References 29 publications

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“…These findings indicate that hyperreactivity of reinnervated arteries to sympathetic activity can be maintained over a prolonged period. Similar functional potentiation at long times after postganglionic lesions was reported by Machida (1929 (Lorez et al 1975;Cowen, MacCormick, Toff, Burnstock & Lumley, 1982;Hill et al 1985;Karanth, Dhital, Springall & Polak, 1990), reinnervation of distant vascular targets (as opposed to sweat glands, Navarro & Kennedy, 1989) after postganglionic lesions appears to be slow (Derom, 1948). As described above, 124 restoration of functional responses may not reflect the anatomical relationships, and responses may be enhanced despite a low innervation density.…”

Section: Discussionsupporting

confidence: 52%

Electrophysiological responses in the rat tail artery during reinnervation following lesions of the sympathetic supply.

Jobling

McLachlan

Jänig

et al. 1992

The Journal of Physiology

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SUMMARY1. Responses to perivascular stimuli have been recorded with intracellular microelectrodes from the smooth muscle of isolated segments of the main caudal artery of rats at various times between 7 and 128 days after all four collector nerve trunks had been lesioned near the base of the tail at 21 days of age.2. In proximal segments (< 40 mm distal to the lesions), excitatory junction potentials (EJPs) and neurogenic tx-depolarizations (NADs) evoked by stimuli presented via a proximally located suction electrode were similar to those in the same segments of unoperated control animals of the same age. Supramaximal EJPs in these segments decreased in amplitude with age.3. Stimuli just supramaximal for EJPs in innervated preparations failed to evoke responses in segments farther than 30-40 mm distal to the lesions at any time after the nerves had been cut and 1 cm excised. Higher voltages evoked slow depolarizing potentials (SDPs) which were of longer time course than EJPs. Similar responses occurred in segments over 60 mm distal to the lesions at 20-50 days after the nerves had been frozen, and in all segments sampled over 100 mm distal to nerve lesions.4. Spontaneous transient depolarizations (STDs) were recorded at all depths of the media in denervated segments. These occurred at frequencies similar to those of spontaneous events (including attenuated spontaneous EJPs) in innervated segments.5. The earliest signs of reinnervation (24-42 days after freeze lesions) consisted of very small amplitude EJPs of normal time course which facilitated markedly during a short train of stimuli (5-10 Hz); these were followed by NADs which were large relative to the amplitudes of the EJPs. 7. Sensitivity to exogenous noradrenaline, assessed in terms of membrane depolarization, was increased in both denervated and reinnervated segments.8. Catecholamine fluorescence disappeared from the arteries at a distance greater than 30-40 mm distal to the site of the nerve lesions. In segments adjacent to those studied electrophysiologically, regenerated fluorescent axons were first visualized at the same postoperative time as the first EJPs were detected. Reinnervation was often patchy in the early stages. When EJPs had regained control amplitude, the density of the perivascular plexus was subjectively assessed as -80 % of control. No regenerated perivascular plexus was detected on the distal parts of the artery, even at 150 days post operation.9. The data show that postganglionic vasoconstrictor axons rapidly regenerate and restore functional contact with their arterial target within a few centimetres of a lesion of a major nerve trunk. EJPs have normal amplitudes but NADs are enhanced compared with controls, even after many months; this may reflect postjunetional supersensitivity. In contrast. distal arterial targets remain denervated for prolonged periods.

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Section: Discussionsupporting

confidence: 52%

Electrophysiological responses in the rat tail artery during reinnervation following lesions of the sympathetic supply.

Jobling

McLachlan

Jänig

et al. 1992

The Journal of Physiology

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“…Our results revealed a far richer variety of innervation within the intervibrissal fur and hairy skin in general than has been revealed in previous studies (Rice and Munger, 1986;Dalsgaard et al, 1989;Kruger et al, 1989;Karanth et al, 1990;Rice et al, 1993;Fundin et al, 1994). In our previous immunofluorescence study of this area using anti-PGP, far more unmyelinated innervation was evident especially to the epidermis and vasculature than had been stained with reduced silver techniques (Rice and Munger, 1986).…”

Section: Discussioncontrasting

confidence: 50%

Comprehensive immunofluorescence and lectin binding analysis of intervibrissal fur innervation in the mystacial pad of the rat

et al. 1997

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The innervation of the intervibrissal fur in the mystacial pad of the rat and mouse was examined by immunofluorescence with a wide variety of antibodies for neuronal related structural proteins, enzymes, and peptides as well as for lectin binding histofluorescence with Griffonia simplicifolia (GSA). Anti-protein gene product 9.5 (PGP) immunofluorescence labeled all sets of axons and endings. The innervation in the upper dermis and epidermis was distributed through a four tiered dermal plexus. From deep to superficial, the second tier was the source of all apparent myelinated mechanoreceptors, the third tier of nearly all the peptidergic and GSA binding innervation, and the fourth tier of nonpeptidergic GSA negative innervation (peptide-/GSA-). Three types of mechanoreceptors-Merkel, transverse lanceolate, and longitudinal lanceolate endings-innervated guard hair follicles. All had similar labeling characteristics for 160 kDa and 200 kDa neurofilament subunits, peripherin, carbonic anhydrase, synaptophysin, and S100. Palisades of longitudinal lanceolate endings were part of piloneural complexes along circumferentially oriented sets of transverse lanceolate endings, peptidergic free nerve endings (FNEs), and peptide-/GSA- FNEs. The longitudinal lanceolate endings were the only mechanoreceptors in the mystacial pad that had detectable calcitonin gene-related peptide. The epidermis contained four types of unmyelinated endings: simple free nerve endings (FNEs), penicillate endings, cluster endings and bush endings. Only the simple FNEs were clearly peptidergic. Virtually all others were peptide-/ GSA-. Each bush ending was actually an intermingled cluster of endings formed by several unmyelinated axons and occasionally an Adelta axon. In contrast to the other unmyelinated innervation to the epidermis, bush endings labeled with an antibody against the Schwann cell protein S100. The necks and mouths of follicles, as well as superficial vasculature, were innervated by a mixture of unmyelinated peptidergic and/or GSA labeled sensory and sympathetic axons. Small presumptive sweat glands were innervated by three sets of peptidergic axons of which one was immunoreactive for somatostatin. Potential functions of the various sets of innervation are discussed.

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“…Thus, the high ratio of CGRP to NPY during the proliferative phase of healing probably represents highly perfused vessels -stimulating tissue regeneration. This temporal shift in CGRP/NPY expression has also been demonstrated in reinnervation of skin flaps, where CGRP emerged at 2 weeks post-operatively, while NPY appeared at week 4 [20].…”

Section: Discussionmentioning

confidence: 89%

Early nerve regeneration after Achilles tendon rupture — a prerequisite for healing? A study in the rat

Ackermann

Ahmed

Kreicbergs

2002

Journal Orthopaedic Research

107

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Nerve regeneration during healing of Achilles tendon rupture in the rat was studied by immunohistocheinistry including semiquantitative assessment. Neuronal markers for regenerating and mature fibers, ie., growth associated protein 43 (GAP-43) and protein gene product 9.5 (PGP 9.5), respectively, were analyzed at different time points (1-16 weeks) post-rupture. In the paratenon, both thc ruptured and intact contralateral tendon (control) consistently exhibited immunoreactivity to the two neuronal markers. However, in the proper tendinous tissue only the ruptured tendon showed immunoreactivity to GAP-43 and PGP 9.5. This expression was seen already at week 1 post-rupture to reach a peak at week 6 followed by a successive drop till week 16. Also the occurrence of sensory and autonomic fibers according to immunorcactivity for calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY), respectively, was analyzed. CGRP-positivity was abundantly seen from weeks 2-6 in both perivascular and sprouting free nerve endings in the proper tendon tissue undergoing healing. NPY appeared later, at weeks 6-8 post-rupture around blood vessels mainly located in the surrounding loose connective tissue. Apart from a role in vasoaction (CGRP, vasodilatory; NPY. vasoconstrictory), both neuropeptides have been implicated in fibroblast and endothelial cell proliferation required for angiogenesis. The present study shows that early healing of ruptured tendons is characterized by an orchestrated, temporal appearance of nerve fibers expressing peptides with different actions. The observed pattern of neuronal regeneration and neuropeptide expression may prove to be important for normal connective tissue healing.

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Reinnervation and neuropeptides in mouse skin flaps

Cited by 48 publications

References 29 publications

Electrophysiological responses in the rat tail artery during reinnervation following lesions of the sympathetic supply.

Electrophysiological responses in the rat tail artery during reinnervation following lesions of the sympathetic supply.

Comprehensive immunofluorescence and lectin binding analysis of intervibrissal fur innervation in the mystacial pad of the rat

Early nerve regeneration after Achilles tendon rupture — a prerequisite for healing? A study in the rat

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