Penttilä H, Waris T, 
      Ashammakhi N,  Vanhatalo S.
      Abstract
        Post-operative survival of arterial grafts is a major challenge in transplantation
          surgery. The vasospasms remain an important cause of graft failures,
          while the understanding about post-operative changes in arterial graft
          innervation is negligible. 
        This study was performed to characterize the neuronal degeneration and
        regeneration in femoral artery grafts transplanted to carotid artery
        in rats. Perivascular innervation was assessed at 1, 3 and 7 days, as
        well as at 1, 3 and 5 months postoperatively. We studied by immunohistochemistry
        markers for neuronal cytoskeleton (neurofilaments and growth associated
        protein-43), parasympathetic innervation (vasoactive intestinal peptide
        (VIP) and neuronal nitrix oxide sybthase (nNOS)), sympathetic innervation
        (tyrosine hydroxylase), as well as endothelial and incudible NOS isoforms. 
        
        During neuronal degeneration, neuropeptide VIP disappeared within the
        first postoperative day, enzymes (nNOS and TH) were vanished by the day
        7, and cytoskeletal neurofilament essentially diappeared after one week.
        During regeneration, the most robust axonal growth, as visualized by
        GAP-43 immunoreactivity, was observed at one month, followed by gradual
        increase in transmitter markers upto three months. Neurofilaments increased
        throughout the five month follow-up period. Major portion of the re-innervating
        nerves proceeded from the proximal carotid artery (host) distally to
        the graft. The primary pathway of axonal regrowth was in arterial adventitial
        layer. The innervation density appeared to be denser in the graft than
        in the host. 
        Our findings suggest that i) the main sequence of neuronal degeneration
        and regeneration in vascular grafts is essentially similar to that reported
        in other tissues, ii) re-innervation of the arterial graft comes mainly
        from the host artery, iii) and the innervation pattern in the graft is
        different from the host. 
        
        Keywords: Arterial graft, transplantation, innervation, degeneration,
        regeneration, vasospasm, sympathetic innervation, free flaps, microsurgery