Liver ischemia-reperfusion injury (LIRI) is associated with an increase in alanine (ALT) and aspartate (AST) aminotransferases levels in the blood, production of proinflammatory cytokines like TNF or IL-1 by immune cells, and reduction in the bile flow. These information are transferred to the brain by vagal and spinal cord visceral afferents. In this study, an attempt was made to reveal the responses of liver related brain structures to 1) the ligation of the hepatic artery for 30 min and 2) the combined ligation of the portal triade (the hepatic artery, portal vein, and bile duct) for 15 min in male Wistar rats. Serum levels of ALT, AST, TNF, and IL-1a were measured and cell activities analysed in the subfornical organ (SFO), suprachiasmatic (SCH), paraventricular (PVN), supraoptic (SON), arcuate (Arc) and ventromedial (VMN) hypothalamic nuclei, parabrachial nucleus (PBN), locus coeruleus (LC), nucleus of the solitary tract (NTS) and A1/C1 catecholaminergic cell groups by counting Fos nuclear immunoreactivity, as a general marker of neuronal activity, 90 min, 5 h and 24 h after the liver reperfusion. Ligation of the portal triade elevated ALT serum level after 90 min and 24 h. Increased AST level was observed only after 24 h in all operated groups of rats. IL-1a serum level was increased only 90 min after ligation of the portal triade. TNF level did not change in any group of rats studied. Ninety minutes after both types of surgeries Fos immunoreactivity was markedly elevated in comparison with sham-operated animals. Five hours after surgeries Fos increased in the PBN and NTS and after 24 hours decreased in all the experimental groups. Obtained data indicate that increased neuronal activity after both types of LIRIs is a primary consequence of the liver damage, but an effect of partial impact of certain non-specific factors can not be also excluded. Anatomical distribution of Fos protein detected after LIRIs gives an opportunity to perform more detailed study, i.e. in the future to identify the specific neuronal phenotypes activated by LIRIs.

This work was supported by grant of the Ministry of Health of the Slovak Republic under project "Stimulation of the vagus nerve as a new method for prevention of ischemia-reperfusion injury of transplanted organs".