title: Neuroprotective effect of melatonin in experimentally induced hypobaric hypoxia.
abstract: Melatonin (MEL) is an endogenous neurohormone with many biological functions, including a powerful antioxidant effect. The aim of the present study was to determine whether MEL protects the brain tissue from the oxidative stress induced by hypobaric hypoxia (HH) in vivo. This study was performed on Wistar rats randomly assigned in four groups, according to the pressure conditions and treatment: Group 1: normoxia and placebo; Group 2: HH and placebo; Group 3: normoxia and MEL; and Group 4: HH and MEL. The following aspects were evaluated: cognitive function (space reference and memory), oxidative stress parameters - serum and brain malondialdehyde (MDA) and reduced glutathione (GSH) levels -, and brain tissue macroscopic and microscopic morphological changes. Exposure to oxidative stress results in cognitive dysfunctions and biochemical alterations: significant increase of MDA and reduction of GSH in both serum and brain tissue. The most important morphological changes were observed in Group 2: increased cellularity, loss of pericellular haloes, shrunken neurons with scanty cytoplasm and hyperchromatic, pyknotic or absent nuclei; reactive gliosis, edema and blood-brain barrier alterations could also be observed in some areas. MEL treatment significantly diminished all these effects. Our results suggest that melatonin is a neuroprotective antioxidant both in normoxia and hypobaric hypoxia that can prevent and counteract the deleterious effects of oxidative stress (neuronal death, reactive astrogliosis, memory impairment and cognitive dysfunctions). Dietary supplements containing melatonin might be useful neuroprotective agents for the therapy of hypoxia-induced consequences.
authors.affiliation: Department of Histology, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania; a_sovrea@yahoo.com.
authors.forename: Corina
authors.initials: C
authors.lastname: Vornicescu
authors.forename: Bianca
authors.initials: B
authors.lastname: Boşca
authors.forename: Doiniţa
authors.initials: D
authors.lastname: Crişan
authors.forename: Sumaya
authors.initials: S
authors.lastname: Yacoob
authors.forename: Nora
authors.initials: N
authors.lastname: Stan
authors.forename: Adriana
authors.initials: A
authors.lastname: Filip
authors.forename: Alina
authors.initials: A
authors.lastname: Şovrea
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D002196:Capillaries / Q000187:drug effects / Q000473:pathology; D002452:Cell Count; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D048430:Cell Shape; D003071:Cognition / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005978:Glutathione / Q000097:blood; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D000860:Hypoxia / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D007150:Immunohistochemistry; D008315:Malondialdehyde / Q000097:blood; D018782:Maze Learning / Q000187:drug effects; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use*; D008568:Memory / Q000187:drug effects; D019581:Neuropil / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D013997:Time Factors
chemical_list: D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D008315:Malondialdehyde; D005978:Glutathione; D008550:Melatonin