The anti-inflammatory and neuroprotective effects of ghrelin in subarachnoid hemorrhage-induced oxidative brain damage in rats

Journal of Neurotrauma

Volumn 27, Issue 6, 2010, Pages 1143-1155

  Erşahin, Mehmet ^a   Toklu, Hale Z ^b   Erzik, Can ^c   Çetinel, Şule ^b   Akakin, Dilek ^b   Velioǧlu Öǧünç, Ayliz ^b   Tetik, Şermin ^b   Özdemir, Zarife N ^b   Şener, Göksel ^b   Yeǧen, Berrak Ç ^b  

^a HAYDARPASA NUMUNE EDUCATION AND RESEARCH HOSPITAL   (Turkey)

^b MARMARA UNIVERSITY   (Turkey)

^c MARMARA UNIVERSITY SCHOOL OF MEDICINE   (Turkey)

Author keywords

cerebral vasospasm; ghrelin; lipid peroxidation; neuron specific enolase; oxidative stress; S 100 ; subarachnoid hemorrhage

Indexed keywords

ADENOSINE TRIPHOSPHATASE (POTASSIUM SODIUM); DNA; GHRELIN; GLUTATHIONE; INTERLEUKIN 1BETA; MALONALDEHYDE; MYELOPEROXIDASE; NEURON SPECIFIC ENOLASE; PROTEIN S100B; REACTIVE OXYGEN METABOLITE; TUMOR NECROSIS FACTOR ALPHA; 1-PHENYL-1,4-EPOXY-1H,4H-NAPHTHO(1,8-DE)(1,2)DIOXEPIN; ENOLASE; NAPHTHALENE DERIVATIVE; NERVE GROWTH FACTOR; NEUROPROTECTIVE AGENT; OXEPINE DERIVATIVE; PROTEIN S 100;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTIINFLAMMATORY ACTIVITY; ARTICLE; BASILAR ARTERY; BLOOD BRAIN BARRIER; BLOOD LEVEL; BRAIN; BRAIN DAMAGE; BRAIN INJURY; BRAIN TISSUE; BRAIN VASOSPASM; BRAIN WATER; CEREBELLUM; CHEMOLUMINESCENCE; CISTERNA MAGNA; CONTROLLED STUDY; DNA FRAGMENTATION; FOREBRAIN; HISTOPATHOLOGY; MALE; MEMORY; NEUROLOGIC EXAMINATION; NEUROPROTECTION; NONHUMAN; RAT; SUBARACHNOID HEMORRHAGE; ANIMAL; BLOOD; DRUG EFFECTS; ENZYME LINKED IMMUNOSORBENT ASSAY; INFLAMMATION; METABOLISM; PATHOPHYSIOLOGY; PHYSIOLOGY; RANDOMIZATION; WISTAR RAT;

ANIMALS; BRAIN; DNA FRAGMENTATION; ENZYME-LINKED IMMUNOSORBENT ASSAY; GHRELIN; INFLAMMATION; INTERLEUKIN-1BETA; MEMORY; NAPHTHALENES; NERVE GROWTH FACTORS; NEUROPROTECTIVE AGENTS; OXEPINS; PHOSPHOPYRUVATE HYDRATASE; RANDOM ALLOCATION; RATS; RATS, WISTAR; REACTIVE OXYGEN SPECIES; S100 CALCIUM BINDING PROTEIN BETA SUBUNIT; S100 PROTEINS; SUBARACHNOID HEMORRHAGE; TUMOR NECROSIS FACTOR-ALPHA;

EID: 77953929950     PISSN: 08977151     EISSN: None     Source Type: Journal    
DOI: 10.1089/neu.2009.1210     Document Type: Article

References (95)

1. Barone, F., Clark, R., Price, W., Price, W.J., White, R.F., Feuerstein, G.Z., Storer, B.L., and Ohlstein, E.H. (1993). Neuronspecific enolase increases in cerebral and systemic circulation following focal ischemia. Brain Res. 623, 77-82.
2. Beaudeux, J.L. (2009). S100B protein: a novel biomarker for the diagnosis of head injury. Ann. Pharm. Fr. 67, 187-194.
3. Belayev, L., Busto, R., Zhao, W., and Ginsberg, M.D. (1996). Quantitative evaluation of blood-brain barrier permeability following middle cerebral artery occlusion in rats. Brain Res. 11, 88-96.
4. Beuge, J.A., and Aust, S.D. (1978). Microsomal lipid peroxidation. Meth. Enzymol. 53, 302-311.
5. Beutler, E., Duron, O., and Kelly, B.M. (1963). Improved method for the determination of blood glutathione. J. Lab. Clin. Med. 61, 882-888.
6. Bradley, P.P., Priebat, D.A., Christersen, R.D., and Rothstei, G. (1982) Measurement of cutaneous inflammation. Estimation of neutrophil content with an enzyme marker. J. Invest. Dermatol. 78, 206-209.
7. Brillault, J. (2008). Hypoxia effects on cell volume and ion uptake of cerebral microvascular endothelial cells. Am. J. Physiol. Cell Physiol. 294, 88-96.
8. Broderick, J.P., Brott, T.G., Duldner, J.E., Tomsick, T., and Leach, A. (1994). Initial and recurrent bleeding are the major causes of death following subarachnoid hemorrhage. Stroke 25, 1342-1347.
9. Brzozowski, T., Konturek, P.C., Sliwowski, Z., Pajdo, R., Drozdowicz, D., Kwiecien, S., Burnat, G., Konturek, S.J., and Pawlik, W.W. (2006). Prostaglandin/cyclooxygenase pathway in ghrelin-induced gastroprotection against ischemia-reperfusion injury. J. Pharmacol. Exp. Ther. 319, 477-487. (Pubitemid 44455155)
10. Burton, K. (1956). A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem. J. 62, 315-323.
11. Cahill, J., and Zhang, J. (2009). Subarachnoid hemorrhage: Is it time for a new direction? Stroke 40, S86-S87.
12. Carlini, V.P., Martini, A.C., Schiöth, H.B., Ruiz, R.D., Fiol De Cuneo, M., and De Barioglio, S.R. (2008). Decreased memory for novel object recognition in chronically food-restricted mice is reversed by acute ghrelin administration. Neuroscience 153, 929-934.
13. Chorny, A., Anderson, P., Gonzalez-Rey, E., and Delgado, M. (2008). Ghrelin protects against experimental sepsis by inhibiting high-mobility group box 1 release and by killing bacteria. J. Immunol. 180, 8369-8377.
14. Cummings, D.E., Weigle, D.S., Frayo, R.S., Breen, P.A., Ma, M.K., Dellinger, E.P., and Purnell, J.Q. (2002). Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N. Engl. J. Med. 346, 1623-1630.
15. Cunningham, R.T., Young, I.S., Winder, J., O'Kane, M.J., McKinstry, S., Johnston, C.F., Dolan, O.M., Hawkins, S.A., and Buchanan, K.D. (1991). Serum neuron specific enolase (NSE) levels as an indicator of neuronal damage in patients with cerebral infarction. Eur. J. Clin. Invest. 21, 497-500.
16. Date, Y., Kojima, M., Hosoda, H., Sawaguchi, A., Mondal, M.S., Suganuma, T., Matsukura, S., Kangawa, K., and Nakazato, M. (2000). Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology 141, 4255-4261.
17. Davies, G.R., Simmonds, N.J., Stevens, T.R.J., Grandison, A., Blake, D.R., and Rampton, D.S. (1992). Mucosal reactive oxygen metabolite production in duodenal ulcer disease. Gut 33, 1467-1472.
18. Delgado, T.J., Brismar, J., and Svendgaard, N.A. (1985). Subarachnoid haemorrhage in the rat: angiography and fluorescence microscopy of the major cerebral arteries. Stroke 16, 595-602.
19. Del Zoppo, G.J., and Hallenbeck, J.M. (2000). Advances in the vascular pathophysiology of ischemic stroke. Thromb. Res. 98, 73-81.
20. Dietrich, H.H., and Dacey, R.G. Jr. (2000). Molecular keys to the problems of cerebral vasospasm. Neurosurgery 46, 517-530.
21. Dixit, V.D., Schaffer, E.M., Pyle, R.S., Collins, G.D., Sakthivel, S.K., Palaniappan, R., Lillard, J.W. Jr., and Taub, D.D. (2004). Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells. J. Clin. Invest. 114, 57-66.
22. Dumont, A.S., Dumont, R.J., Chow, M.M., Lin, C.L., Calisaneller, T., Ley, K.F., Kassell, N.F., and Lee, K.S. (2003). Cerebral vasospasm after subarachnoid hemorrhage: putative role of inflammation. Neurosurgery 53, 123-133; discussion 133-135.
23. Erecinska, M., Cherian, S., and Silver, I.A. (2004). Energy metabolism in mammalian brain during development. Prog Neurobiol. 73, 397-445.
24. Erşahin, M., Toklu, H.Z., Cetinel, S., Yüksel, M., Yegen, B.C., and Sener, G. (2009). Melatonin reduces experimental subarachnoid hemorrhage-induced oxidative brain damage and neurological symptoms. J. Pineal Res. 46, 324-332.
25. Fiske, C.H., and Subbarow, Y. (1925). The colorimetric determination of phosphorus. J. Biol. Chem. 66, 375-400.
26. Foroutan, S., Brillault, J., Forbush, B., and O'Donnell, M.E. (2005). Moderate-to-severe ischemic conditions increase activity and phosphorylation of the cerebral microvascular endothelial cell Na+-K+-Cl- cotransporter. Am. J. Physiol. Cell Physiol. 289, 1492-1501.
27. Franzon, R., Lamers, M.L., Stefanello, F.M., Wannmacher, C.M., Wajner, M., and Wyse, A.T. (2003). Evidence that oxidative stress is involved in the inhibitory effect of proline on Na(+),K(+)-ATPase activity in synaptic plasma membrane of rat hippocampus. Int. J. Dev. Neurosci. 21, 303-307.
28. Gnanapavan, S., Kola, B., Bustin, S.A., Morris, D.G., McGee, P., Fairclough, P., Bhattacharya, S., Carpenter, R., Grossman, A.B., and Korbonits, M. (2002). The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J. Clin. Endocrinol. Metab. 87, 2988-2991.
29. Gonzalez-rey, E., Chorny, A., and Delgado, M. (2006). Therapeutic action of ghrelin in a mouse model of colitis. Gastroenterology 130, 1707-1720.
30. Granado, M., Priego T., Martin, A.I., Villanua, A., and Lopez-Caldron, A. (2005). Anti-inflammatory effect of the ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) in arthritic rats. Am. J. Physiol. 288, E486-E492.
31. Hardemark, H., Ericsson, N., Kotwica, Z., Rundström, G., Mendel-Hartvig, I., Olsson, Y., Påhlman, S., and Persson, L. (1989). S-100 protein and neuron-specific enolase in CSF after experimental traumatic or focal ischemic brain damage. J. Neurosurg. 71, 727-731.
32. Hardemark, H., Persson, L., Bolander, H., Hillered, L., Olsson, Y., and Pahlman, S. (1988). Neuronspecific enolase is a marker of cerebral ischemia and infarct size in rat cerebrospinal fluid. Stroke 19, 1140-1144.
33. Hatfield, R., and McKernan, R. (1992). CSF neuron-specific enolase as a quantitative marker of neuronal damage in a rat stroke model. Brain Res. 577, 249-252.
34. Hattori, N., Saito, T., Yagyu, T, Jiang, B.H., Kitagawa, K., and Inagaki, C. (2001). GH, GH receptor, GH secretagogue receptor, and ghrelin expression in human T cells, B cells, and neutrophils. J. Clin. Endocrinol. Metab. 86, 4284-4291.
35. Herrmann, M., Curio, N., Jost, S.,Wunderlich, M.T., Synowitz, H., and Wallesch, C.W. (1999). Protein S-100B and neuron specific enolase as early neurobiochemical markers of the severity of traumatic brain injury. Restor. Neurol. Neurosci. 14, 109-114.
36. Hillegass, L.M., Griswold, D.E., Brickson, B., and Albrightson-Winslow, C. (1990). Assessment of myeloperoxidase activity in whole rat kidney. J. Pharmacol. Meth. 24, 285-295.
37. Horn, M., Segar, F., and Schlote, W. (1995). Neuron-specific enolase in gerbil brain and serum after transient cerebral ischemia. Stroke 26, 290-296.
38. Horvath, T.L., Diano, S., Sotonyi, P., and Heiman, M. (2001). Ghrelin and the regulation of energy balance-a hypothalamic perspective. Endocrinology 142, 4163-4169.
39. Huber, J.D., Egleton, R.D., and Davis, T.P. (2001). Molecular physiology and pathophysiology of tight junctions in the blood-brain barrier. Trends. Neurosci. 24, 719-725.
40. Hütter, B.O., Kreitschmann-Andermahr, I., and Gilsbach, J.M. (2001). Health-related quality of life after aneurysmal subarachnoid hemorrhage: impacts of bleeding severity, computerized tomography findings, surgery, vasospasm, and neurological grade. J. Neurosurg. 94, 241-251.
41. Imperatore, C., Germanò , A., d'Avella, D., Tomasello, F., and Costa, G. (2000). Effects of the radical scavenger AVS on behavioral and BBB changes after experimental subarachnoid hemorrhage. Life Sci. 21, 779-790.
42. Iseri, S.O., Sener, G., Saglam, B., Ercan, F., Gedik, N., and Yegen, B.C. (2008). Ghrelin alleviates biliary obstruction-induced chronic hepatic injury in rats. Regul. Pept. 7, 73-79.
43. Kaiser, E., Kuzmits, R., Pregant, P., Burghuber, O., and Worofka, W., (1989). Clinical biochemistry of neuron specific enolase. Clinica Chimica Acta 183, 13-31.
44. Kamezaki, T., Yanaka, K., Nagase, S., Fujita, K., Kato, N., and Nose, T. (2002). Increased levels of lipid peroxides as predictive of symptomatic vasospasm and poor outcome after aneurysmal subarachnoid hemorrhage. J. Neurosurg. 97, 1302-1305.
45. Kasimay, O., Iseri, S.O., Barlas, A., Bangir, D., Yegen, C., Arbak, S., and Yegen, B.C. (2006). Ghrelin ameliorates pancreaticobiliary inflammation and associated remote organ injury in rats. Hepatol. Res. 36, 11-19.
46. Kojima, M., Hosoda, H., Date, Y., Nakazato, M., Matsuo, H., and Kangawa, K. (1999). Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402, 656-660.
47. Kolias, A.G., Sen, J., and Belli, A. (2009). Pathogenesis of cerebral vasospasm following aneurysmal subarachnoid hemorrhage: putative mechanisms and novel approaches. J. Neurosci. Res. 87, 1-11.
48. Kurella, E., Kukley, M., Tyulina, O., Dobrota, D., Matejovicova, M., Mezesova, V., and Boldyrev, A. (1997). Kinetic parameters of Na/K-ATPase modified by free radicals in vitro and in vivo. Ann. N.Y. Acad. Sci. 3, 661-665.
49. Liu, Y., Wang, P.S., Xie, D., Liu, K., and Chen, L. (2006). Ghrelin reduces injury of hippocampal neurons in a rat model of cerebral ischemia/reperfusion. Chin. J. Physiol. 49, 244-250.
50. Li, W.G., Gavrila, D., Liu, X., Wang, L., Gunnlaugsson, S., Stoll, L.L., McCormick, M.L., Sigmund, C.D., Tang, C., and Weintraub, N.L. (2004). Ghrelin inhibits proinflammatory responses and nuclear factor-kappaB activation in human endothelial cells. Circulation 109, 2221-2226.
51. Lowry, O.H., Rosenbrough, N.J., Farr, A.L., and Randall, R.J. (1951). Protein measurements with the folin phenol reagent. J. Biol. Chem. 193, 265-275.
52. Lu, H., Zhang, D.M., Chen, H.L., Lin, Y.X., Hang, C.H., Yin, H.X., and Shi, J.X. (2009). N-acetylcysteine suppresses oxidative stress in experimental rats with subarachnoid hemorrhage. J. Clin. Neurosci. 16, 684-688.
53. Marangos, P., Zomzely-Neurath, C., and York, C. (1976). Determination and characterization of neuron specific protein (NSP) associated enolase activity. Biochem. Biophys. Res. Commun. 68, 1309-1316.
54. Marzatico, F., Gaetani, P., Buratti, E., Messina, A.L., Ferlenga, P., Rodriguez, Y., and Baena, R. (1990). Effects of high-dose methylprednisolone on Na(+)-K+ATPase and lipid peroxidation after experimental subarachnoid hemorrhage. Acta Neurol. Scand. 82, 263-270.
55. Mayer, S.A., and Linares, G. (2009). Can a simple blood test quantify brain injury? Crit. Care. 13, 166.
56. McKee, K.K., Tan, C.P., Palyha, O.C., Liu, J., Feighner, S.D., Hreniuk, D.L., Smith, R.G., Howard, A.D., and Van Der Ploeg, L.H. (1997). Cloning and characterization of two human G protein-coupled receptor genes (GPR38 and GPR39) related to the growth hormone secretagogue and neurotensin receptors. Genomics 46, 426-434.
57. Miao, Y., Xia, Q., Hou, Z., Zheng, Y., Pan, H., and Zhu, S. (2007). Ghrelin protects cortical neuron against focal ischemia/ reperfusion in rats. Biochem. Biophys. Res. Commun. 359, 795-800.
58. Munakata, A., Ohkuma, H., Nakano, T., Shimamura, N., Asano, K., and Naraoka, M. (2009). Effect of a free radical scavenger, edaravone, in the treatment of patients with aneurysmal subarachnoid hemorrhage. Neurosurgery 64, 423-428.
59. Obay, B.D., Tasdemir, E., Tümer, C., Bilgin, H.M., and Atmaca, M. (2008). Dose dependent effects of ghrelin on pentylenetetrazole-induced oxidative stress in a rat seizure model. Peptides 29, 448-455.
60. Oertel, M., Schumacher, U., McArthur, D.L., Kästner, S., and Böker, D.K. (2006). S-100B and NSE: markers of initial impact of subarachnoid haemorrhage and their relation to vasospasm and outcome. J. Clin. Neurosci. 13, 834-840.
61. Ohara, Y., Peterson, T.E., and Harrison, D.G. (1993). Hypercholesterolemia increases endothelial superoxide anion production. J. Clin. Invest. 91, 2546-2551.
62. Ostrowski, R.P., Colohan, A.R., and Zhang, J.H. (2006). Molecular mechanisms of early brain injury after subarachnoid hemorrhage. Neurol. Res. 28, 399-414.
63. Panikashvili, D., Shein, N.A., Mechoulam, R., Trembovler, V., Kohen, R., Alexandrovich, A., and Shohami, E. (2006). The endocannabinoid 2-AG protects the blood-brain barrier after closed head injury and inhibits mRNA expression of proinflammatory cytokines. Neurobiol. Dis. 22, 257-264.
64. Park, S., Yamaguchi, M., Zhou, C., Calvert, J.W., Tang, J., and Zhang, J.H. (2004). Neurovascular protection reduces early brain injury after subarachnoid hemorrhage. Stroke 35, 2412-2417.
65. Persson, L., Hardemark, H.G., Gustafsson, J., Rundstrom, G., Mendel-Hartvig, I., Esscher, T., and Pahlman, S. (1987). S-100 protein and neuron-specific enolase in cerebrospinal fluid and serum: markers of cell damage in human central nervous system. Stroke 18, 911-918.
66. Pyne-Geithman, G.J., Caudell, D.N., Prakash, P., and Clark, J.F. (2009). Glutathione peroxidase and subarachnoid hemorrhage: implications for the role of oxidative stress in cerebral vasospasm. Neurol. Res. 31, 195-199.
67. Raabe, A., Grolms, C., Sorge, O., Zimmermann, M., and Seifert, V. (1999). Fatal secondary increase in serum S-100B protein after severe head injury. Report of three cases. Neurosurgery 45, 477-483.
68. Rabinowicz, A.L., Correale, J., Boutros, R.B., Couldwell, W.T., Henderson, C.W., and DeGiorgio, C.M. (1996). Neuron-specific enolase is increased after single seizures during inpatient video/EEG monitoring. Epilepsia 37, 122-125.
69. Reading, H.W., and Isbir, T. (1980). The role of cation activated ATPase in transmitter release from the rat iris. Q.J. Exp. Physiol. 65, 105-116.
70. Reiter, R.J., Tan, D.X., Manchester, L.C., and Qi, W. (2001). Biochemical reactivity of melatonin with reactive oxygen and nitrogen species: a review of the evidence. Cell Biochem. Biophys. 34, 237-256.
71. Rothermundt, M., Peters, M., Prehn, J.H., and Arolt, V. (2003). S100B in brain damage and neurodegeneration. Microsc. Res. Tech. 15, 614-632.
72. Sabri, M., Kawashima, A., Ai, J., and Macdonald, R.L. (2008). Neuronal and astrocytic apoptosis after subarachnoid hemorrhage: a possible cause for poor prognosis. Brain Res. 1238, 163-171.
73. Sano, K., Asano, T., Tanishima, T., and Sasaki, T. (1980). Lipid peroxidation as a cause of cerebral vasospasm. Neurol. Res. 2, 253-272.
74. Santos, M.S., Moreno, A.J., and Carvalho, A.P. (1996). Relationships between ATP depletion, membrane potential, and the release of neurotransmitters in rat nerve terminals. An in vitro study under conditions that mimic anoxia, hypoglycemia, and ischemia. Stroke 27, 941-950.
75. Sehirli, O., Sener, E., Sener, G., Cetinel, S., Erzik, C., and Yegen, B.C. (2008). Ghrelin improves burn-induced multiple organ injury by depressing neutrophil infiltration and the release of pro-inflammatory cytokines. Peptides 29, 1231-1240.
76. Sercombe, R., Dinh, Y.R., and Gomis, P. (2002). Cerebrovascular inflammation following subarachnoid hemorrhage. Jpn. J. Pharmacol. 88, 227-249.
77. Shah, K.G., Wu, R., Jacob, A., Blau, S.A., Ji, Y., Dong, W., Marini, C.P., Ravikumar, T.S., Cappa, G.F., and Wang, P. (2009). Human ghrelin ameliorate organ injury and improves survival after radiation injury combined with severe sepsis. Mol. Med. 15, 407-414.
78. Steinberg, R., Gueniau, C., Scarna, H., Keller, A., Worcel, M., and Pujol, J.F. (1984). Experimental brain ischemia: Neuronspecific enolase level in cerebrospinal fluid as an index of neuronal damage. J. Neurochem. 43, 19-24.
79. Stroick, M., Fatar, M., Ragoschke-Schumm, A., Fassbender, K., Bertsch, T., and Hennerici, M.G. (2006). Protein S-100B-a prognostic marker for cerebral damage. Curr. Med. Chem. 13, 3053-3060.
80. Takata, K., Sheng, H., Borel, C.O., Laskowitz, D.T., Warner, D.S., and Lombard, F.W. (2008). Long-term cognitive dysfunction following experimental subarachnoid hemorrhage: new perspectives. Exp. Neurol. 213, 336-344.
81. Theil, M.M., Miyake, S., Mizuno, M., Tomi, C., Croxford, J.L., Hosoda, H., Theil, J., Von Hörsten, S., Yokote, H., Chiba, A., Lin, Y., Oki, S., Akamizu, T., Kangawa, K., and Yamamura, T. (2009). Suppression of experimental autoimmune encephalomyelitis by ghrelin. J. Immunol. 183, 2859-2866.
82. Toklu, H.Z., Hakan, T., Biber, N., Solakoglu, S., Ogünç, A.V., and Sener, G. (2009b).The protective effect of alpha lipoic acid against traumatic brain injury in rats. Free Radic. Res. 43, 658-667.
83. Toklu, H.Z., Uysal, M.K., Kabasakal, L., Sirvanci, S., Ercan, F., and Kaya, M. (2009a).The effects of riluzole on neurological, brain biochemical, and histological changes in early and late term of sepsis in rats. J. Surg. Res. 152, 238-248.
84. Tonnesen, M.G., Worthen, G.S., and Johnston, R.B. (1988). Neutrophil emigration, activation, and tissue damage. in: The Molecular and Cellular Biology of Wound Repair. R.A.E. Clark and P.M. Hensen (eds), Plenum: New York, pps. 149-184.
85. Tóth, K., László, K., Lukács, E., and Lénárd, L. (2009). Intraamygdaloid microinjection of acylated-ghrelin influences passive avoidance learning. Behav. Brain Res. 14, 308-311.
86. Townend, W., and Ingebrigtsen, T. (2006). Head injury outcome prediction: a role for protein S-100B? Injury 37, 1098-1108.
87. Ukkola, O. (2009). Ghrelin and metabolic disorders. Curr. Protein Pept. Sci. 10, 2-7.
88. Wassem, T., Duxbury, M., Ito, H., Ashley, S.W., and Robinson, M.K. (2008). Exogeneous ghrelin modulates release of proand anti-inflammatory cytokines in LPS-stimulated macrophages through distinct signaling pathways. Surgery 143, 334-342.
89. Wedmore, C.V., and Williams, J.T. (1981). Control of vascular permeability by polymorphonuclear leukocytes in inflammation. Nature 289, 646-650.
90. Whitton, P.S. (2007). Inflammation as a causative factor in the aetiology of Parkinson's disease. Br. J. Pharmacol. 150, 963-976.
91. Wu, R., Dong, W., Ji, Y., Zhou, M., Marini, C.P., Ravikumar, T.S., and Wang, P. (2008). Orexigenic hormone ghrelin attenuates local and remote organ injury after intestinal ischemiareperfusion. PLoS One 3, e2026.
92. Wyllie, H. (1980). Glucocorticoid induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 284, 555-556.
93. Xu, J., Wang, S., Lin, Y., Cao, L., Wang, R., and Chi, Z. (2009). Ghrelin protects against cell death of hippocampal neurons in pilocarpine-induced seizures in rats. Neurosci. Lett. 27, 58-61.
94. Yu, F., Sugawara, T., and Chan, P.H. (2003). Treatment with dihydroethidium reduces infarct size after transient focal cerebral ischemia in mice. Brain Res. 18, 223-227.
95. Zubkov, A.Y., and Rabinstein, A.A. (2009). Medical management of cerebral vasospasm: present and future. Neurol. Res. 31, 626-631.