title: Melatonin Counteracts at a Transcriptional Level the Inflammatory and Apoptotic Response Secondary to Ischemic Brain Injury Induced by Middle Cerebral Artery Blockade in Aging Rats.
abstract: Aging increases oxidative stress and inflammation. Melatonin counteracts inflammation and apoptosis. This study investigated the possible protective effect of melatonin on the inflammatory and apoptotic response secondary to ischemia induced by blockade of the right middle cerebral artery (MCA) in aging male Wistar rats. Animals were subjected to MCA obstruction. After 24 h or 7 days of procedure, 14-month-old nontreated and treated rats with a daily dose of 10 mg/kg melatonin were sacrificed and right and left hippocampus and cortex were collected. Rats aged 2 and 6 months, respectively, were subjected to the same brain injury protocol, but they were not treated with melatonin. mRNA expression of interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), Bcl-2-associated death promoter (BAD), Bcl-2-associated X protein (BAX), glial fibrillary acidic protein (GFAP), B-cell lymphoma 2 (Bcl-2), and sirtuin 1 was measured by reverse transcription-polymerase chain reaction. In nontreated animals, a significant time-dependent increase in IL-1β, TNF-α, BAD, and BAX was observed in the ischemic area of both hippocampus and cortex, and to a lesser extent in the contralateral hemisphere. Hippocampal GFAP was also significantly elevated, while Bcl-2 and sirtuin 1 decreased significantly in response to ischemia. Aging aggravated these changes. Melatonin administration was able to reverse significantly these alterations. In conclusion, melatonin may ameliorate the age-dependent inflammatory and apoptotic response secondary to ischemic cerebral injury.
authors.affiliation: Department of Physiology, School of Medicine, Complutense University of Madrid , Madrid, Spain .
authors.forename: Sergio D
authors.initials: SD
authors.lastname: Paredes
authors.affiliation: Department of Biochemistry and Molecular Biology III, School of Medicine, Complutense University of Madrid , Madrid, Spain .
authors.forename: Lisa
authors.initials: L
authors.lastname: Rancan
authors.affiliation: Instituto de Investigación Biomédica de Vigo (IBIV), Xerencia de Xestión Integrada de Vigo, SERGAS, Biomedical Research Unit, Hospital Rebullón (CHUVI) , Vigo, Spain .
authors.forename: Roman
authors.initials: R
authors.lastname: Kireev
authors.affiliation: Department of Biochemistry and Molecular Biology III, School of Medicine, Complutense University of Madrid , Madrid, Spain .
authors.forename: Alberto
authors.initials: A
authors.lastname: González
authors.affiliation: Department of Biochemistry and Molecular Biology III, School of Medicine, Complutense University of Madrid , Madrid, Spain .
authors.forename: Pedro
authors.initials: P
authors.lastname: Louzao
authors.affiliation: Experimental Medicine and Surgery Unit, Hospital Clínico San Carlos , Madrid, Spain .
authors.forename: Pablo
authors.initials: P
authors.lastname: González
authors.affiliation: Experimental Medicine and Surgery Unit, Hospital Clínico San Carlos , Madrid, Spain .
authors.forename: Cruz
authors.initials: C
authors.lastname: Rodríguez-Bobada
authors.affiliation: Department of Biochemistry and Molecular Biology III, School of Medicine, Complutense University of Madrid , Madrid, Spain .
authors.forename: Cruz
authors.initials: C
authors.lastname: García
authors.affiliation: Department of Biochemistry and Molecular Biology III, School of Medicine, Complutense University of Madrid , Madrid, Spain .
authors.forename: Elena
authors.initials: E
authors.lastname: Vara
authors.affiliation: Department of Physiology, School of Medicine, Complutense University of Madrid , Madrid, Spain .
authors.forename: Jesús A F
authors.initials: JA
authors.lastname: Tresguerres
keywords: aging; brain; ischemia; melatonin; middle cerebral artery blockade