Effect of Liver Ischemia–Reperfusion Injury on the Activity of Neurons in the Rat Brain

Abstract

Liver ischemia-reperfusion injury (LIRI) influences different body cells. Little is known about the effect of LIRI on the activity of neurons. Response of neurons to: (1) single ligation of hepatic artery (LIRIa) for 30 min and (2) combined ligation of portal triade (common hepatic artery, portal vein, common bile duct, LIRIb) for 15 min was investigated in Wistar rats. Ninety minutes, 5 h, and 24 h after liver reperfusion, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), interleukin 1alpha (IL-1alpha), and tumor necrosis factor alpha (TNFalpha) serum levels were analyzed and Fos-immunolabeled cells counted in subfornical organ (SFO), suprachiasmatic (SCH), paraventricular (PVN), supraoptic (SON), arcuate (ARC), and ventromedial (VMN) hypothalamic nuclei, locus coeruleus (LC), nucleus of the solitary tract (NTS), and A1/C1 catecholaminergic cell groups. LIRIb increased ALT serum level after 90 min and 24 h while AST activity only after 24 h in all experimental groups. IL-1alpha serum level was increased only after 90 min of LIRIb while TNFalpha level did not change. Ninety minutes after surgeries more Fos-immunostained cells occurred in both LIRIs than sham-operated animals in all structures studied. More distinct Fos expression occurred after LIRIb than LIRIa in SON, PVN, VMN, and NTS. Five hours after both LIRIs, Fos increased in the parabrachial nucleus (PBN) and NTS. Twenty-four hours after both LIRIs Fos incidence decreased in all groups. Although the present data indicate that increased neuronal activity after both LIRIs is mainly a consequence of the liver damage itself partial impact of non-specific factors can not be excluded. However, the anatomical distribution of Fos occurrence detected after LIRIs gives great opportunity to perform a targeted phenotypic identification of the activated neurons by LIRIs in the subsequent experiments.

Exosomes Mediate Hippocampal and Cortical Neuronal Injury Induced by Hepatic Ischemia-Reperfusion Injury through Activating Pyroptosis in Rats

“…Besides, accumulating studies of cerebral stroke, ischemia, or hemorrhagic have reported that the selective inhibitor of caspase-1, AC-YVAD-CMK, was proved to have a therapeutic effect and pyroptosis was involved in the pathophysiological process [40, 49–51]. A previously published study found that the activity of cells in specific brain structures, anatomically or functionally associated with the liver, was reflected by Fos immunoreactivity and showed an increase under HIRI condition [52]. Besides, IL-1 β administration could also increase neuronal activations, which was showed by Fos immunoreactivity [53].…”

Activation of Different Neuronal Phenotypes in the Rat Brain Induced by Liver Ischemia–Reperfusion Injury: Dual Fos/Neuropeptide Immunohistochemistry

“…The parasympathetic nerves innervating the liver originate from the pre-ganglionic neurons in the dorsal motor nucleus of the vagus (DMV) located in the dorsal brainstem, however, no clear intrahepatic post-ganglionic neurons have been identified (Berthoud 2004). Previously we have shown (Pirnik et al 2009) that both models of LIRI activate Fos in a number of neurons in different brain structures. However, they are prominently activated mainly in the PVN, SON, and NTS/A2 and A1/C1 areas.…”

“…Therefore, the purpose of this research was to extend our previous data (Pirnik et al 2009) dealing with mapping the anatomical distribution of Fos expression in response to LIRI by employing a dual Fos/neuropeptide immunohistochemistry. Our attempt was to perform a targeted phenotypic neuronal detection in several brain areas related to the liver functioning in male Wistar rats after 90 min, 5, and 24 h of: (i) a single ligation of the hepatic artery for 30 min and (ii) combined ligation of the portal triad (the common hepatic artery, portal vein, and common bile duct) for 15 min.…”

“…Our attempt was to perform a targeted phenotypic neuronal detection in several brain areas related to the liver functioning in male Wistar rats after 90 min, 5, and 24 h of: (i) a single ligation of the hepatic artery for 30 min and (ii) combined ligation of the portal triad (the common hepatic artery, portal vein, and common bile duct) for 15 min. These two models were chosen based on the findings in our previous study (Pirnik et al 2009) completed with data from the literature (Steiner and Martinez 1961;Li et al 2003).…”