title: Liver regeneration: immunohistochemical study of intrinsic hepatic innervation after partial hepatectomy in rats.
abstract: BACKGROUND
  We examined the intrinsic hepatic innervation after partial hepatectomy (PH) in rats and the presence and pattern of neural sprouting in regenerating liver.
  
  
  METHODS
  Male Wistar rats (age 9-13 weeks-w, weight 204-356 g), were submitted to two-thirds PH. Rats were sacrificed at postoperative days (d) 1, 3, 5, 7, at 2 and 4 w, and at 3 and 6 months (m) (6-7 animals/group, control group n = 4). Immunohistochemistry for the pan-neural marker protein gene product 9.5 (PGP9.5) and growth-associated protein 43 (GAP-43), a marker of regenerating nerve axons, was performed on tissue sections from the R1 lobe of the regenerating liver. Portal tracts (PTs) with immunoreactive fibers were counted in each section and computer-assisted morphometric analysis (Image Pro Plus) was used to measure nerve fiber density (number of immuno-positive nerve fibers/mm2 (40x)).
  
  
  RESULTS
  Immunoreactivity for PGP9.5 was positive in all groups. The number of PGP9.5 (+) nerve fibers decreased from 0.32 +/- 0.12 (control group) to 0.18 +/- 0.09 (1d post-PH group), and gradually increased reaching pre-PH levels at 6 m (0.3 +/- 0.01). In contrast, immunoreactivity for GAP-43 was observed at 5d post-PH, and GAP-43 (+) PTs percentage increased thereafter with a peak at 3 m post-PH. GAP-43 (+) nerve fiber density increased gradually from 5d (0.05 +/- 0.06) with a peak at 3 m post-PH (0.21 +/- 0.027). At 6 m post-PH, immunoreactivity for GAP-43 was not detectable.
  
  
  CONCLUSIONS
  Following PH in rats: 1) nerve fiber density in portal tracts decreases temporarily, and 2) neural sprouting in the regenerating liver lobes starts at 5d, reaches peak levels at 3 m and disappears at 6 m post-PH, indicating that the increase in hepatic mass after PH provides an adequate stimulus for the sprouting process.
authors.forename: Apostolos N
authors.initials: AN
authors.lastname: Kandilis
authors.forename: John
authors.initials: J
authors.lastname: Koskinas
authors.forename: Ioannis
authors.initials: I
authors.lastname: Vlachos
authors.forename: Spyridon
authors.initials: S
authors.lastname: Skaltsas
authors.forename: Despina
authors.initials: D
authors.lastname: Karandrea
authors.forename: Petros
authors.initials: P
authors.lastname: Karakitsos
authors.forename: Alkistis
authors.initials: A
authors.lastname: Pantopoulou
authors.forename: Marina
authors.initials: M
authors.lastname: Palaiologou
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Nikiteas
authors.forename: Dina G
authors.initials: DG
authors.lastname: Tiniakos
authors.forename: Despina N
authors.initials: DN
authors.lastname: Perrea
mesh_terms: D000818:Animals; D001369:Axons / Q000737:chemistry / Q000502:physiology; D015415:Biomarkers / Q000032:analysis; D019922:GAP-43 Protein / Q000032:analysis; D006498:Hepatectomy; D007150:Immunohistochemistry; D008099:Liver / Q000294:innervation*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D009412:Nerve Fibers / Q000737:chemistry / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology*; D017208:Rats, Wistar; D043222:Ubiquitin Thiolesterase / Q000032:analysis
chemical_list: D015415:Biomarkers; D019922:GAP-43 Protein; C489034:UCHL1 protein, rat; D043222:Ubiquitin Thiolesterase