Melatonin reduces experimental subarachnoid hemorrhage-induced oxidative brain damage and neurological symptoms.
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.
Ersahin
Mehmet
M
Department of Neurosurgery, Haydarpasa Numune Education and Research Hospital, Istanbul, Turkey.
Toklu
Hale Z
HZ
Cetinel
Sule
S
Yüksel
Meral
M
Yeğen
Berrak C
BC
Sener
Göksel
G
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
D000975:Antioxidants; D018696:Neuroprotective Agents; D008550:Melatonin