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Open AccessArticle

Comparison of the Effect of Melatonin Treatment before and after Brain Ischemic Injury in the Inflammatory and Apoptotic Response in Aged Rats

1
Department of Biochemistry and Molecular Biology, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain
2
Department of Physiology, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain
3
Research Unit, Hospital Clínico San Carlos, 28040 Madrid, Spain
4
Biomedical Research Foundation, Hospital Clínico San Carlos, 28040 Madrid, Spain
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
The last two authors share senior authorship.
Int. J. Mol. Sci. 2018, 19(7), 2097; https://doi.org/10.3390/ijms19072097
Received: 3 June 2018 / Revised: 12 July 2018 / Accepted: 16 July 2018 / Published: 19 July 2018
(This article belongs to the Special Issue Immunosenescence and Related Processes)
Aging is associated with an increase in stroke risk. Melatonin, a potent free radical scavenger and broad spectrum antioxidant, has been shown to counteract inflammation and apoptosis in brain injury. However, little is known on the possible protective effects of melatonin in aged individuals affected by brain ischemia. Also, using melatonin before or after an ischemic stroke may result in significantly different molecular outcomes. The objective of the present study was to compare the effects of pre-ischemia vs. post-ischemia melatonin administration in an ischemic lesion in the cortex and hippocampus of senescent Wistar rats. An obstruction of the middle cerebral artery (MCA) to 18-month-old animals was performed. In general, animals treated with melatonin from 24 h prior to surgery until 7 days after the surgical procedure (PrevT) experienced a significant decrease in the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), glial fibrillary acidic protein (GFAP), Bcl-2-associated death promoter (BAD), and Bcl-2-associated X protein (BAX) in both cortex and hippocampus, while hippocampal levels of sirtuin 1 (SIRT1) and B-cell lymphoma 2 (Bcl-2) increased. Treatment of animals with melatonin only after surgery (AT) resulted in similar effects, but to a lesser extent than in the PrevT group. In any case, melatonin acted as a valuable therapeutic agent protecting aged animals from the harmful effects of cerebral infarction. View Full-Text
Keywords: aging; brain; ischemia; melatonin; middle cerebral artery blockade aging; brain; ischemia; melatonin; middle cerebral artery blockade
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Rancan, L.; Paredes, S.D.; García, C.; González, P.; Rodríguez-Bobada, C.; Calvo-Soto, M.; Hyacinthe, B.; Vara, E.; Tresguerres, J.A.F. Comparison of the Effect of Melatonin Treatment before and after Brain Ischemic Injury in the Inflammatory and Apoptotic Response in Aged Rats. Int. J. Mol. Sci. 2018, 19, 2097.

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