The density of hepatic autonomic innervation differs between compensatory and direct hyperplasia rat models

To contribute to the knowledge of the autonomic innervation in liver regeneration, here we investigate the distribution of tyrosine hydroxylase (TH)- and choline acetyltransferase (ChAT)-like immunoreactive (LI) nerve fibers, to indicate noradrenergic and cholinergic nerves, respectively, in rats under different conditions of liver damage and repair. By immunohistochemistry and assessment of nerve fiber density, three models of induced hepatic regeneration were examined: the carbon tetrachloride (CCl₄ ) intoxication, with two treatment periods of 14 weeks and 18 weeks; the partial hepatectomy (PH); the thyroid hormone (T3) treatment. TH- and ChAT-LI nerve fibers were detectable mostly in the portal spaces, the TH-LI ones occurring only around blood vessels while the ChAT-LI nerve fibers were also associated with secretory ducts. The density of TH-like immunoreactivity in the portal areas decreased after the CCl₄ 14 weeks treatment and PH and increased after T3. By contrast, ChAT-LI nerve fibers appeared particularly abundant around the neoductal elements in the CCl₄ rats and were rare to absent in the PH and T3-treated groups. The ChAT-LI nerve fiber density within the portal areas revealed an increase in the CCl₄ -treated rats while showing no change in the PH and T3-treated rats. The changes in the density of perivascular TH- and ChAT-containing nerve fibers suggest a finely tuned autonomic modulation of hepatic blood flow depending on the type of subacute/chronic induced hyperplasia, while the characteristic occurrence of the periductal cholinergic innervation after the CCl₄ treatment implies a selective parasympathetic role in regulating the physiopathological regenerative potential of the rat liver.