Opposite effects of pinealectomy and melatonin administration on brain damage following cerebral focal ischemia in rat

The endocrine system has been recognized as an important factor that may co ntribute to the outcome of stroke. We tested in rats the hypothesis that th e pineal gland and/or its hormone melatonin may affect the outcome of a tra nsient cerebral arteries occlusion (CerAO). Reversible 90 min focal ischemi a was produced using a three-vessel occlusion method. Surgically or sham pi nealectomized rats were exposed to CerAO 15 days after surgery. Melatonin ( 4 x 2.5 mg/kg: 30 min prior to onset of CerAO, immediately after recirculat ion was established, and 1 and 2 hr later) or its vehicle were administered intraperitoneally. The outcome of CerAO was assessed by quantitative assay of DNA damage or by Nissl staining and measurement of the infarct volume. Pinealectomy increased both the extent of DNA damage and the infarct volume ; administration of melatonin to pinealectomized rats reduced both these ma rkers of brain injury. We propose that the pineal endocrine system may infl uence the outcome of stroke. The mechanism of action and the pathophysiolog ical role of this system, e.g., in aging, should be further characterized.