title: Melatonin reduces experimental subarachnoid hemorrhage-induced oxidative brain damage and neurological symptoms.
abstract: Oxidative stress has detrimental effects in several models of neurodegenerative diseases, including subarachnoid hemorrhage (SAH). This study investigated the putative neuroprotective effect of melatonin, a powerful antioxidant, in a rat model of SAH. Male Wistar albino rats were divided as control, vehicle-treated SAH, and melatonin-treated (10 mg/kg, i.p.) SAH groups. To induce SAH, 0.3 mL blood was injected into cisterna magna of rats. Forty-eight hours after SAH induction, neurological examination scores were measured and the rats were decapitated. Brain tissue samples were taken for blood-brain barrier (BBB) permeability, brain water content, histological examination, or determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO), and Na+-K+-ATPase activities. Formation of reactive oxygen species in brain tissue samples was monitored by using a chemiluminescence (CL) technique. The neurological examination scores were increased in SAH groups on the second day of SAH induction and SAH caused a significant decrease in brain GSH content and Na+-K+-ATPase activity, which was accompanied with significant increases in CL, MDA levels, and MPO activity. On the other hand, melatonin treatment reversed all these biochemical indices as well as SAH-induced histopathological alterations, while increased brain water content and impaired BBB were also reversed by melatonin treatment. This study suggests that melatonin, which can easily cross BBB, alleviates SAH-induced oxidative stress and exerts neuroprotection by preserving BBB permeability and by reducing brain edema.
authors.affiliation: Department of Neurosurgery, Haydarpasa Numune Education and Research Hospital, Istanbul, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Ersahin
authors.forename: Hale Z
authors.initials: HZ
authors.lastname: Toklu
authors.forename: Sule
authors.initials: S
authors.lastname: Cetinel
authors.forename: Meral
authors.initials: M
authors.lastname: Yüksel
authors.forename: Berrak C
authors.initials: BC
authors.lastname: Yeğen
authors.forename: Göksel
authors.initials: G
authors.lastname: Sener
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001488:Basilar Artery / Q000648:ultrastructure; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008550:Melatonin / Q000494:pharmacology* / Q000627:therapeutic use; D046529:Microscopy, Electron, Transmission; D009460:Neurologic Examination; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000975:Antioxidants; D018696:Neuroprotective Agents; D008550:Melatonin