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Proc Natl Acad Sci USA 1996; 93:14140-14145. 57. Ribelayga C, Gauer F, Pévet P et al. Photoneural regulation of rat pineal hydroxyindole-Omethyltransferase (HIOMT) messenger ribonucleic acid expression: An analysis of its complex relationship with HIOMT activity. Endocrinology 1999; 140:1375-1384. 58. Ribelayga C, Pévet P, Simonneaux V. Adrenergic and peptidergic regulations of hydroxyindole-Omethyltransferase in rat pineal gland. Brain Res 1997; 777:247-250. 12 Melatonin: Biological Basis of Its Function in Health and Disease CHAPTER 2 Oxidative Stress-Mediated Damage during in Vivo Ischemia-Reperfusion Injury: Protective Effects of Melatonin Russel J.

J Pineal Res 2003; 34:40-52. 59. Sener G, Sehirli AO, Paskaloglu K et al. Melatonin treatment protects against ischemia/reperfusion induced functional and biochemical changes in rat urinary bladder. J Pineal Res 2003; 34:226-230. 60. Sener G, Sehirli AO, Keyer-Uysol M et al. The protective effect of melatonin on renal ischemia-reperfusion injury in the rat. J Pineal Res 2002; 32:120-126. 61. Inci I, Inci D, Dutly A et al. Melatonin attenuates posttransplant lung ischemia-reperfusion injury. Ann Thorac Surg 2002; 73:220-223.

The endpoints in this study included infarct volume and the number of apoptotic cells in the brain. 37 A relative melatonin deficiency may not be the only consequence of pinealectomy. Thus, loss of the pineal gland may alter arterial blood pressure, cerebral blood flow, arterial blood gases, hemodynamic parameters and the hematocrit, all of which could impact the degree of cerebral damage during I/R. 38 In intact rats as well, providing supplemental melatonin before interrupting blood flow to the brain as well as during reperfusion attenuates the resulting brain damage.

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