Melatonin promotes myelination by decreasing white matter inflammation after neonatal stroke.
Melatonin demonstrates neuroprotective properties in adult models of cerebral ischemia, acting as a potent antioxidant and anti-inflammatory agent. We investigated the effect of melatonin in a 7-d-old rat model of ischemia-reperfusion, leading to both cortical infarct and injury in the underlying white matter observed using MRI and immunohistochemistry. Melatonin was given i.p. as either a single dose before ischemia or a double-dose regimen, combining one before ischemia and one 24 h after reperfusion. At 48 h after injury, neither a significant reduction in cortical infarct volume nor a variation in the number of TUNEL- and nitrotyrosine-positive cells within the ipsilateral lesion was observed in melatonin-treated animals compared with controls. However, a decrease in the density of tomato lectin-positive cells after melatonin treatment was found in the white matter underlying cortical lesion. Furthermore, we showed a marked increase in the myelin basic protein-immunoreactivity in the cingulum and in the density of mature oligodendrocytes (APC-immunoreactive) in both the ipsilateral cingulum and external capsule. These results suggest that melatonin is not able to reduce cortical infarct volume in a neonatal stroke model but strongly reduces inflammation and promotes subsequent myelination in the white matter.
Villapol
Sonia
S
INSERM AVENIR R05230HS (U676), Université Paris, Faculté de Médecine Denis Diderot, 75019 Paris, France.
Fau
Sébastien
S
Renolleau
Sylvain
S
Biran
Valérie
V
Charriaut-Marlangue
Christiane
C
Baud
Olivier
O
D000818:Animals; D020520:Brain Infarction / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008550:Melatonin / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D004676:Myelin Basic Protein / Q000276:immunology / Q000378:metabolism; D009186:Myelin Sheath / Q000187:drug effects*; D009187:Myelitis / Q000188:drug therapy* / Q000209:etiology; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D009836:Oligodendroglia / Q000166:cytology; D037121:Plant Lectins; D051381:Rats; D015427:Reperfusion Injury / Q000150:complications*
D004676:Myelin Basic Protein; D018696:Neuroprotective Agents; D037121:Plant Lectins; C034981:tomato lectin; D008550:Melatonin