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

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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 1α (IL-1α), and tumor necrosis factor α (TNFα) 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-1α serum level was increased only after 90 min of LIRIb while TNFα 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.

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Acknowledgments

The authors wish to thank to Institute of Laboratory Diagnostic (Alpha medical, Bratislava, SR) for determination of ALT and AST serum activities. Fos antiserum (No. 94012) was provided by Dr. Jens Mikkelsen (NeuroSearch A/S Ballerup, Denmark). This work was supported by grant of the Ministry of Health of the Slovak Republic under the project MZ 2006/19-SAV-01 entitled “Stimulation of the vagus nerve as a new method for prevention of ischemia–reperfusion injury of transplanted organs” and VEGA grant 1/4312/07.

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Pirnik, Z., Bundzikova, J., Francisty, T. et al. Effect of Liver Ischemia–Reperfusion Injury on the Activity of Neurons in the Rat Brain. Cell Mol Neurobiol 29, 951–960 (2009). https://doi.org/10.1007/s10571-009-9381-7

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