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.
Similar content being viewed by others
References
Aoe T, Inaba H, Kon S, Imai M, Aono M, Mizuguchi T, Saito T, Nishino T (1997) Heat shock protein 70 messenger RNA reflects the severity of ischemia/hypoxia-reperfusion injury in the perfused rat liver. Crit Care Med 25:324–329
Bailey SM, Reinke LA (2000) Effect of low flow ischemia-reperfusion injury on liver function. Life Sci 66:1033–1044
Berthoud HR (2004) Anatomy and function of sensory hepatic nerves. Anat Rec A Discov Mol Cell Evol Biol 280:827–835
Berthoud HR, Neuhuber WL (2000) Functional and chemical anatomy of the afferent vagal system. Auton Neurosci 85:1–17
Bonaz B, Taché Y (1997) Corticotropin-releasing factor and systemic capsaicin-sensitive afferents are involved in abdominal surgery-induced Fos expression in the paraventricular nucleus of the hypothalamus. Brain Res 748:12–20
Bonnet MS, Pecchi E, Trouslard J, Jean A, Dallaporta M, Troadec JD (2009) Central nesfatin-1-expressing neurons are sensitive to peripheral inflammatory stimulus. J Neuroinflamm 6:27
Crockett ET, Spielman W, Dowlatshahi S, He J (2006) Sex differences in inflammatory cytokine production in hepatic ischemia-reperfusion. J Inflamm (Lond) 3:16
Duval H, Mbatchi SF, Grandadam S, Legendre C, Loyer P, Ribault C, Piquet-Pellorce C, Guguen-Guillouzo C, Boudjema K, Corlu A (2010) Reperfusion stress induced during intermittent selective clamping accelerates rat liver regeneration through JNK pathway. J Hepatol 52:560–569
Eum HA, Cha YN, Lee SM (2007) Necrosis and apoptosis: sequence of liver damage following reperfusion after 60 min ischemia in rats. Biochem Biophys Res Commun 358:500–505
Frangogiannis NG (2007) Chemokines in ischemia and reperfusion. Thromb Haemost 97:738–747
Girn HR, Ahilathirunayagam S, Mavor AI, Homer-Vanniasinkam S (2007) Reperfusion syndrome: cellular mechanisms of microvascular dysfunction and potential therapeutic strategies. Vasc Endovascular Surg 41:277–293
Gourcerol G, Gallas S, Mounien L, Leblanc I, Bizet P, Boutelet I, Leroi AM, Ducrotte P, Vaudry H, Jegou S (2007) Gastric electrical stimulation modulates hypothalamic corticotropin-releasing factor-producing neurons during post-operative ileus in rat. Neuroscience 148:775–781
Grindstaff RJ, Grindstaff RR, Cunningham JT (2000) Baroreceptor sensitivity of rat supraoptic vasopressin neurons involves noncholinergic neurons in the DBB. Am J Physiol Regul Integr Comp Physiol 279:R1934–R1943
Gu GB, Ju G (1995) The parabrachio-subfornical organ projection in the rat. Brain Res Bull 38:41–47
Han F, Zhang YF, Li YQ (2003) Fos expression in tyrosine hydroxylase-containing neurons in rat brainstem after visceral noxious stimulation: an immunohistochemical study. World J Gastroenterol 9:1045–1050
Hokfelt T, Johansson O, Goldstein M (1984) Central catecholamine neurons as revealed by immunohistochemistry with special reference to adrenaline neurons. In: Bjorklund A, Hokfelt T (eds) Handbook of chemical neuroanatomy, vol 2. Elsevier, Amsterdam, pp 157–276
Ionescu DA, Lugoji G, Radula D (1986) The nucleus of the solitary tract: a review of its anatomy and functions, with emphasis on its role in a putative central-control of brain-capillaries permeability. Neurol Psychiatr (Bucur) 24:69–85
Jaeschke H, Bautista AP, Spolarics Z, Spitzer JJ (1992) Superoxide generation by neutrophils and Kupffer cells during in vivo reperfusion after hepatic ischemia in rats. J Leukoc Biol 52:377–382
Kaur C, You Y, Singh J, Peng CM, Ling EA (2001) Expression of Fos immunoreactivity in some catecholaminergic brainstem neurons in rats following high-altitude exposure. J Neurosci Res 63:54–63
Kiss A, Aguilera G (1992) Participation of alpha 1-adrenergic receptors in the secretion of hypothalamic corticotropin-releasing hormone during stress. Neuroendocrinology 56:153–160
Kiss A, Søderman A, Bundzikova J, Pirnik Z, Mikkelsen JD (2006) Zolpidem, a selective GABAA receptor α1 subunit agonist, induces Fos expression in oxytocinergic neurons of the hypothalamic paraventricular and accessory but not supraoptic nuclei in the rat. Brain Res Bull 71:200–207
Kobashi M, Adachi A (1986) Projection of nucleus tractus solitarius units influenced by hepatoportal afferent signal to parabrachial nucleus. J Auton Nerv Syst 16:153–158
Krukoff TL, MacTavish D, Harris KH, Jhamandas JH (1995) Changes in blood volume and pressure induce c-fos expression in brainstem neurons that project to the paraventricular nucleus of the hypothalamus. Brain Res Mol Brain Res 34:99–108
Lacroix S, Rivest S (1997) Functional circuitry in the brain of immune-challenged rats: partial involvement of prostaglandins. J Comp Neurol 387:307–324
Li AJ, Ritter S (2004) Glukoprivation increases expression of neuropeptide Y mRNA in hindbrain neurons that innervate hypothalamus. Eur J Neurosci 19:2147–2154
Li SQ, Liang LJ, Huang JF, Li Z (2003) Hepatocyte apoptosis induced by hepatic ischemia-reperfusion injury in cirrhotic rats. Hepatobiliary Pancreat Dis Int 2(1):102–105
Luo X, Kiss A, Makara G, Lolait SJ, Aguilera G (1994) Stress-specific regulation of corticotropin releasing hormone receptor expression in the paraventricular and supraoptic nuclei of the hypothalamus in the rat. J Neuroendocrinol 6:689–696
Martins PN, Neuhaus P (2007) Surgical anatomy of the liver, hepatic vasculature and bile ducts in the rat. Liver Int 27:384–392
Mikkelsen JD, Vrang N, Mrosovsky N (1998) Expression of Fos in the circadian system following nonphotic stimulation. Brain Res Bull 47:367–376
Miyatake Y, Ikeda H, Michimataa R, Koizumia S, Ishizua A, Nishimura N, Yoshiki T (2004) Differential modulation of gene expression among rat tissues with warm ischemia. Exp Mol Pathol 77:222–230
Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates. Academic Press, New York, USA
Pirnik Z, Kiss A (2005) Fos expression variances in mouse hypothalamus upon physical and osmotic stimuli: Co-staining with vasopressin, oxytocin, and tyrosine hydroxylase. Brain Res Bull 65:423–431
Pirnik Z, Mravec B, Kiss A (2004a) Fos protein expression in mouse hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei upon osmotic stimulus: colocalization with vasopressin, oxytocin, and tyrosine hydroxylase. Neurochem Int 45:597–607
Pirnik Z, Mravec B, Kubovcakova L, Mikkelsen JD, Kiss A (2004b) Hypertonic saline and immobilization induce Fos expression in mouse brain catecholaminergic cell groups: colocalization with tyrosine hydroxylase and neuropeptide Y. Ann N Y Acad Sci 1018:398–404
Pirnik Z, Bundzikova J, Francisty T, Cibulova E, Lackovicova L, Mravec B, Kiss A (2009) Effect of ischemia-reperfusion of liver on the activity of neurons in the rat brain. Cell Mol Neurobiol 29:951–960
Rhodes CH, Morrell JI, Pfaff DW (1981) Immunohistochemical analysis of magnocellular elements in rat hypothalamus: distribution and numbers of cells containing neurophysin, oxytocin, and vasopressin. J Comp Neurol 198:45–64
Ritter S, Llewellyn-Smith I, Dinh TT (1998) Subgroups of hindbrain catecholamine neurons are selectively activated by 2-deoxy-d-glucose induced metabolic challenge. Brain Res 805:41–54
Romani F, Vertemati M, Frangi M, Aseni P, Monti R, Codeghini A, Belli L (1988) Effect of superoxide dismutase on liver ischemia-reperfusion injury in the rat: a biochemical monitoring. Eur Surg Res 20:335–340
Shioda S, Nakai Y (1996) Direct projections form catecholaminergic neurons in the caudal ventrolateral medulla to vasopressin-containing neurons in the supraoptic nucleus: a triple-labeling electron microscope study in the rat. Neurosci Lett 221:45–48
Shioda S, Shimoda Y, Nakai Y (1992) Ultrastructural studies of medullary synaptic inputs to vasopressin-immunoreactive neurons in the supraoptic nucleus of the rat hypothalamus. Neurosci Lett 148:155–158
Spiegel HU, Bahde R (2006) Experimental models of temporary normothermic liver ischemia. J Invest Surg 19:113–123
Stanley S, Pinto S, Segal J, Pérez CA, Viale A, DeFalco J, Cai X, Heisler LK, Friedman JM (2010) Identification of neuronal subpopulations that project from hypothalamus to both liver and adipose tissue polysynaptically. Proc Natl Acad Sci USA 107:7024–7029
Steiner PE, Martinez JB (1961) Effects on the rat liver of bile duct, portal vein and hepatic artery ligations. Am J Pathol 39:257–289
Sved AF, Mancini DL, Graham JC, Schreihofer AM, Hoffman GE (1994) PNMT-containing neurons of the C1 cell group express c-fos in response to changes in baroreceptor input. Am J Physiol 266:R361–R367
Swanson LW, Kuypers HG (1980) The paraventricular nucleus of the hypothalamus: cytoarchitectonic subdivisions and organization of projections to the pituitary, dorsal vagal complex, and spinal cord as demonstrated by retrograde fluorescence double-labeling methods. J Comp Neurol 194:555–570
Swanson LW, Sawchenko PE, Wiegand SJ, Price JL (1980) Separate neurons in the paraventricular nucleus project to the median eminence and to the medulla or spinal cord. Brain Res 198:190–195
Teoh NC, Farrell GC (2003) Hepatic ischemia reperfusion injury: pathogenic mechanisms and basis for hepatoprotection. J Gastroenterol Hepatol 18:891–902
Uyama N, Geerts A, Reynaert H (2004) Neural connections between the hypothalamus and the liver. Anat Rec A Discov Mol Cell Evol Biol 280:808–820
Walsh KB, Toledo AH, Rivera-Chavez FA, Lopez-Neblina F, Toledo-Pereyra LH (2009) Inflammatory mediators of liver ischemia–reperfusion injury. Exp Clin Transpl 7:78–93
Wanner GA, Ertel W, Müller P, Höfer Y, Leiderer R, Menger MD, Messme K (1996) Liver ischemia and reperfusion induces a systemic inflammatory response through Kupffer cell activation. Shock 5:34–40
Xiao JS, Cai FG, Niu Y, Zhang Y, Xu XL, Ye QF (2005) Preconditioning effects on expression of proto-oncogenes c-fos and c-jun after hepatic ischemia/reperfusion in rats. Hepatobiliary Pancreat Dis Int 4:197–202
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”.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10571-010-9621-x