title: Degeneration and regeneration of perivascular innervation in arterial grafts.
abstract: Because the understanding of postoperative changes in arterial graft innervation is limited, this study was performed to characterize neuronal degeneration and regeneration events immunohistochemically in femoral arterial grafts transplanted to carotid arteries in rats. Specimens taken 1 day, 3 days, 7 days, 1 month, 3 months, and 5 months after surgery were assessed for vasoactive intestinal peptide, neurofilaments, growth-associated protein 43, tyrosine hydroxylase, and nitric oxide synthase isoenzymes. During neuronal degeneration, vasoactive intestinal peptide disappeared within 1 day, transmitter-synthesizing enzymes (nitric oxide synthase and tyrosine hydroxylase) had vanished by day 7, and neurofilaments (cytoskeletal markers) had essentially disappeared after 1 week. In the regeneration phase, the most robust axonal growth, as visualized by growth-associated protein 43, was observed at 1 month, followed by a gradual increase in neurotransmitter markers at 1 and 3 months, whereas the neurofilaments increased gradually up to the end of the 5-month observation period. Reinnervation proceeded from the proximal carotid (host) trunk distally to the graft. Axonal re-growth occurred mainly in arterial adventitia. Innervation density, as visually assessed, was denser in the graft than in the host. These findings suggest that 1) the main sequence of degeneration and regeneration follows that reported in other models of neuronal degeneration; 2) reinnervation of the arterial grafts comes mainly from the host arteries; and 3) the innervation density in the graft may differ from that in the host, which may suggest target-derived regulation of innervation. The latter finding may have clinical implications. It suggests that for a good outcome it would be beneficial to choose a sparsely innervated graft rather than a densely innervated one.
authors.affiliation: Department of Oral and Maxillofacial Diseases, Surgical Hospital, Helsinki University Central Hospital, Helsinki, Finland. heikki.penttila@fimnet.fi
authors.forename: Penttilä
authors.initials: P
authors.lastname: Heikki
authors.forename: Waris
authors.initials: W
authors.lastname: Timo
authors.forename: Ashammakhi
authors.initials: A
authors.lastname: Nureddin
authors.forename: Vanhatalo
authors.initials: V
authors.lastname: Sampsa
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000166:cytology / Q000378:metabolism; D002339:Carotid Arteries / Q000294:innervation* / Q000378:metabolism / Q000601:surgery*; D005260:Female; D005263:Femoral Artery / Q000294:innervation* / Q000378:metabolism / Q000637:transplantation*; D005500:Follow-Up Studies; D019922:GAP-43 Protein / Q000378:metabolism; D007150:Immunohistochemistry; D007527:Isoenzymes; D009410:Nerve Degeneration; D009416:Nerve Regeneration / Q000502:physiology*; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
chemical_list: D019922:GAP-43 Protein; D007527:Isoenzymes; D016900:Neurofilament Proteins; D014660:Vasoactive Intestinal Peptide; D019001:Nitric Oxide Synthase; D014446:Tyrosine 3-Monooxygenase