Anatomy of efferent hepatic nerves

Abstract

The role of neural elements in regulating blood flow through the hepatic sinusoids, solute exchange, and parenchymal function is incompletely understood. This is due in part to limited investigation in only a few species whose hepatic innervation may differ significantly from humans. For example, most experimental studies have used rats and mice having livers with little or no intralobular innervation. In contrast, most other mammals, including humans, have aminergic and peptidergic nerves extending from perivascular plexus in the portal space into the lobule, where they course in Disse's space in close relationship to stellate cells (fat storing cells of Ito) and hepatic parenchymal cells. While these fibers extend throughout the lobule, they predominate in the periportal region. Cholinergic innervation, however, appears to be restricted to structures in the portal space and immediately adjacent hepatic parenchymal cells. Neuropeptides have been colocalized with neurotransmitters in both adrenergic and cholinergic nerves. Neuropeptide Y (NPY) has been colocalized in aminergic nerves supplying all segments of the hepatic-portal venous and the hepatic arterial and biliary systems. Nerve fibers immunoreactive for substance P and somatostatin follow a similar distribution. Intralobular distribution of all of these nerve fibers is species-dependent and similar to that reported for aminergic fibers. Vasoactive intestinal peptide and calcitonin gene-related peptide (CGRP) are reported to coexist in cholinergic and sensory afferent nerves innervating portal veins and hepatic arteries and their branches, but not the other vascular segments or the bile ducts. Nitrergic nerves immunoreactive for neuronal nitric oxide (nNOS) are located in the portal tract where nNOS colocalizes with both NPY-and CGRP-containing fibers. In summary, the liver is innervated by aminergic, cholinergic, peptidergic, and nitrergic nerves. While innervation of structures in the portal tract is relatively similar between species, the extent and distribution of intralobular innervation are highly variable as well as species-dependent and may be inversely related to the density of gap junctions between contiguous hepatic parenchymal cells. 2004 Wiley-Liss, Inc.

Hepatic Stellate Cells Support Hematopoiesis and are Liver-Resident Mesenchymal Stem Cells

“…This niche of stellate cells displays similarities to the perivascular hematopoietic stem cell niche in the bone marrow and may favor homing of migrating hematopoietic stem/progenitor cells and extramedullary hematopoiesis in the liver. Stellate cells are closely associated with nerve fibers of the peripheral nervous system as reported for bone marrow MSC and can integrate signals from the sympathetic nervous system [3,4,21,22,23]. Furthermore, bone marrow MSC and hepatic stellate cells can be activated by external stimuli such as hypoxia and release cytokines like vascular endothelial growth factor, hepatocyte growth factor, angiopoietins and insulin-like growth factors, in order to modulate the behavior of other cell types such as endothelial cells [24,25,26,27,28].…”

Central insulin-mediated regulation of hepatic glucose production [Review]

“…Efferent vagal nerve fibers synapse with postganglionic neurons in the hepatic portal region parasympathetic ganglia, and distribute themselves in the periportal area where active gluconeogenesis takes place within the hepatic lobules [38,39]. Besides regulating HGP, the vagus nerve is known to be closely involved sue, and body weight, and even displayed insulin resistance [20].…”

Hepatic stem cell niches

“…Jagged 1 appears during the activation of stellate cells (72), which further indicates that activated stellate cells can also provide a suitable environment for hepatic progenitor cells. Nerve endings are also found close to stellate cells in the liver (111). Hepatic stellate cells can directly respond to perivascular nerve stimulation through the release of the osmolyte myoinositol and exhibit Ca 2+ transients in response to phenylephrine (112,113).…”