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

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Abstract

The aim of the present study was to reveal the effect of liver ischemia–reperfusion injury (LIRI) on the activity of selected neuronal phenotypes in rat brain by applying dual Fos-oxytocin (OXY), vasopressin (AVP), tyrosine hydroxylase (TH), phenylethanolamine N-methyltransferase (PNMT), corticoliberine (CRH), and neuropeptide Y (NPY) immunohistochemistry. Two liver ischemia–reperfusion models were investigated: (i) single ligation of the hepatic artery (LIRIa) for 30 min and (ii) combined ligation of the portal triad (the common hepatic artery, portal vein, and common bile duct) (LIRIb) for 15 min. The animals were killed 90 min, 5 h, and 24 h after reperfusion. Intact and sham operated rats served as controls. As indicated by semiquantitative estimation, increases in the number of Fos-positive cells mainly occurred 90 min after both liver reperfusion injuries, including activation of AVP and OXY perikarya in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, and TH, NPY, and PNMT perikarya in the catecholaminergic ventrolateral medullar A1/C1 area. Moreover, only PNMT perikarya located in the A1/C1 cell group exhibited increased Fos expression 5 h after LIRIb reperfusion. No or very low Fos expression was found 24 h after reperfusion in neuronal phenotypes studied. Our results show that both models of the LIRI activate, almost by the same effectiveness, a number of different neuronal phenotypes which stimulation may be associated with a complex of physiological responses induced by (1) surgery (NPY, TH, PNMT), (2) hemodynamic changes (AVP, OXY, TH, PNMT), (3) inflammation evoked by ischemia and subsequent reperfusion (TH), and (4) glucoprivation induced by fasting (NPY, PNMT, TH). All these events may contribute by different strength to the development of pathological alterations occurring during the liver ischemia–reperfusion injury.

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Acknowledgments

The authors would like to thank Dr. Jens D. Mikkelsen and Dr. Greti Aguilera for the kind providing Fos, NPY, TH, OXY and AVP, CRH, PNMT antibodies, respectively. This study was supported by grant of the Ministry of Health of the Slovak Republic (MZ 2006/19-SAV-01) entitled “Stimulation of the vagus nerve as a new method for prevention of ischemia–reperfusion injury of transplanted organs”.

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Bundzikova, J., Pirnik, Z., Lackovicova, L. et al. Activation of Different Neuronal Phenotypes in the Rat Brain Induced by Liver Ischemia–Reperfusion Injury: Dual Fos/Neuropeptide Immunohistochemistry. Cell Mol Neurobiol 31, 293–301 (2011). https://doi.org/10.1007/s10571-010-9621-x

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