INSERM AVENIR R05230HS (U676), Université Paris, Faculté de Médecine Denis Diderot, 75019 Paris, France.
Pediatr Res. 2011 Jan;69(1):51-5. doi: 10.1203/PDR.0b013e3181fcb40b.
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.
褪黑素在成人脑缺血模型中表现出神经保护特性，作为一种有效的抗氧化剂和抗炎剂。我们研究了褪黑素在 7 日龄大鼠缺血再灌注模型中的作用，通过 MRI 和免疫组织化学观察到皮质梗死和皮质下白质损伤。褪黑素通过腹腔注射给药，要么在缺血前给予单次剂量，要么给予双重剂量方案，即在缺血前给予一次，再灌注后 24 小时再给予一次。在损伤后 48 小时，与对照组相比，褪黑素治疗组的皮质梗死体积无明显减少，同侧病变内 TUNEL 和硝基酪氨酸阳性细胞的数量也没有变化。然而，在白质下皮质病变下，褪黑素处理后番茄凝集素阳性细胞的密度降低。此外，我们还发现，在扣带和外囊的同侧扣带中，髓鞘碱性蛋白免疫反应性显著增加，成熟少突胶质细胞（APC 免疫反应性）的密度也增加。这些结果表明，褪黑素不能减少新生儿中风模型中的皮质梗死体积，但能强烈减轻炎症，并促进白质的随后髓鞘形成。
