Transient effect of melatonin treatment after neonatal hypoxic-ischemic brain injury in rats

Autoři: Hester Rijkje Berger aff001;  Axel K. G. Nyman aff003;  Tora Sund Morken aff005;  Marius Widerøe aff003
Působiště autorů: Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway aff001;  Department of Pediatrics, St. Olav University Hospital, Trondheim, Norway aff002;  Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway aff003;  Department of Neurology, St. Olav University Hospital, Trondheim, Norway aff004;  Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway aff005;  Department of Ophthalmology, St. Olav University Hospital, Trondheim, Norway aff006
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225788


Melatonin has potential neuroprotective capabilities after neonatal hypoxia-ischemia (HI), but long-term effects have not been investigated. We hypothesized that melatonin treatment directly after HI could protect against early and delayed brain injury. Unilateral HI brain injury was induced in postnatal day 7 rats. An intraperitoneal injection of either melatonin or vehicle was given at 0, 6 and 25 hours after hypoxia. In-vivo MRI was performed 1, 7, 20 and 43 days after HI, followed by histological analysis. Forelimb asymmetry and memory were assessed at 12–15 and at 36–43 days after HI. More melatonin treated than vehicle treated animals (54.5% vs 15.8%) developed a mild injury characterized by diffusion tensor values, brain volumes, histological scores and behavioral parameters closer to sham. However, on average, melatonin treatment resulted only in a tendency towards milder injury on T2-weighted MRI and apparent diffusion coefficient maps day 1 after HI, and not improved long-term outcome. These results indicate that the melatonin treatment regimen of 3 injections of 10 mg/kg within the first 25 hours only gave a transient and subtle neuroprotective effect, and may not have been sufficient to mitigate long-term brain injury development following HI.

Klíčová slova:

Brain damage – corpus callosum – Diffusion tensor imaging – Histology – Hypoxia – Magnetic resonance imaging – Medical hypoxia – Melatonin


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