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首页> 外文期刊>The European Journal of Neuroscience >Minocycline attenuates hypoxia-ischemia-induced neurological dysfunction and brain injury in the juvenile rat.
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Minocycline attenuates hypoxia-ischemia-induced neurological dysfunction and brain injury in the juvenile rat.

机译:米诺环素减轻幼鼠缺氧缺血性神经功能障碍和脑损伤。

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摘要

To investigate whether minocycline provides long-lasting protection against neonatal hypoxia-ischemia-induced brain injury and neurobehavioral deficits, minocycline was administered intraperitoneally in postnatal day 4 Sprague-Dawley rats subjected to bilateral carotid artery occlusion followed by exposure to hypoxia (8% oxygen for 15 min). Brain injury and myelination were examined on postnatal day 21 (P21) and tests for neurobehavioral toxicity were performed from P3 to P21. Hypoxic-ischemic insults resulted in severe white matter injury, enlarged ventricles, deficits in the hippocampus, reduction in numbers of mature oligodendrocytes and tyrosine hydroxylase-positive neurons, damage to axons and dendrites, and impaired myelination, as indicated by the decrease in myelin basic protein immunostaining in the P21 rat brain. Hypoxic-ischemic insult also significantly affected physical development (body weight gain and eye opening) and neurobehavioral performance, including sensorimotor and locomotor function, anxiety and cognitive ability in the P21 rat. Treatments with minocycline significantly attenuated the hypoxia-ischemia-induced brain injury and improved neurobehavioral performance. The protection of minocycline was associated with its ability to reduce microglial activation. The present results show that minocycline has long-lasting protective effects in the neonatal rat brain in terms of both hypoxia-ischemia-induced brain injury and the associated neurological dysfunction.
机译:为了研究米诺环素是否对新生儿缺氧缺血性脑损伤和神经行为缺陷提供长期保护,在出生后第4天对Sprague-Dawley大鼠进行了腹膜内给予米诺环素治疗,使其双侧颈动脉闭塞,然后暴露于低氧(8%氧气15分钟)。在出生后第21天(P21)检查脑损伤和髓鞘形成,并在P3至P21进行神经行为毒性测试。缺氧缺血性损伤导致严重的白质损伤,脑室扩大,海马缺陷,成熟少突胶质细胞和酪氨酸羟化酶阳性神经元数量减少,轴突和树突损伤以及髓鞘受损,如髓鞘碱性减少P21大鼠大脑中的蛋白质免疫染色。缺氧缺血性损伤也显着影响P21大鼠的身体发育(体重增加和睁眼)和神经行为表现,包括感觉运动和运动功能,焦虑和认知能力。用米诺环素治疗可显着减轻缺氧缺血性脑损伤并改善神经行为表现。米诺环素的保护与其减少小胶质细胞活化的能力有关。目前的结果表明,就缺氧缺血引起的脑损伤和相关的神经功能障碍而言,米诺环素对新生大鼠脑具有长期的保护作用。

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