α-Phenyl-n-tert-butyl-nitrone ameliorates hippocampal injury and improves learning and memory in juvenile rats following neonatal exposure to lipopolysaccharide
α-Phenyl-n-tert-butyl-nitrone ameliorates hippocampal injury and improves learning and memory in juvenile rats following neonatal exposure to lipopolysaccharide
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DOI：
10.1111/j.1460-9568.2008.06121.x
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发表时间：
2008-03-01
影响因子：
3.4
通讯作者：
Cai, Zhengwei
中科院分区：
文献类型：
--
作者：
Fan, Lir-Wan;Tien, Lu-Tai;Cai, Zhengwei
新生儿接触传染源可能会导致长期的神经功能障碍，尤其与随后出现的运动和认知障碍有关。我们之前的研究表明，暴露于脂多糖（LPS）后用α-苯基-正叔丁基硝酮（PBN）治疗可减少新生大鼠LPS引起的脑损伤。为了检查 PBN 是否具有持久的保护作用并改善 LPS 引起的运动和认知功能障碍，在出生后第 5 天 (P5) 的 Sprague-Dawley 幼鼠脑内注射 LPS (1 mg/kg) 5 分钟后，腹腔内注射 PBN (100 mg/kg)。 P3至P21进行神经行为测试，并在注射LPS后24小时和16天检查脑损伤。与对照大鼠相比，新生儿 LPS 暴露导致旷场任务中从 P13 到 P17 的过度活跃。 P21 时仍可观察到的神经行为缺陷包括平衡木行走和杆测试中的功能障碍、被动回避任务中的学习和记忆缺陷以及高架十字迷宫任务中较少的焦虑样反应。这些行为结果与 LPS 诱导的中背侧海马 (HP) CA1 区轴突损伤、HP 大小和中背侧 HP CA1 区神经元数量减少、黑质和腹侧被盖区神经元酪氨酸羟化酶免疫反应性丧失相匹配。 PBN 治疗提供了针对 LPS 诱导的轴突损伤和神经元损失的持久保护，并改善了幼年大鼠的相关神经功能障碍。
Neonatal exposure to infectious agents may result in long-term neurological disability, and is particularly associated with the subsequent development of motor and cognitive disturbances. Our previous studies have shown that treatment with alpha-phenyl-n-tert-butyl-nitrone (PBN) following exposure to lipopolysaccharide (LPS) reduces LPS-induced brain injury in the neonatal rat. To examine whether PBN has long-lasting protective effects and ameliorates LPS-induced motor and cognitive dysfunction, PBN (100 mg/kg) was administered intraperitoneally 5 min after an LPS (1 mg/kg) intracerebral injection in postnatal day 5 (P5) Sprague-Dawley rat pups. Neurobehavioral tests were carried out from P3 to P21, and brain injury was examined at 24 h and 16 days after LPS injection. Neonatal LPS exposure resulted in hyperactivity from P13 to P17 in the open field task as compared with the control rat. Neurobehavioral deficits that were still observable at P21 included dysfunction in the beam-walking and pole tests, learning and memory deficits in the passive avoidance task, and less anxiety-like response in the elevated plus-maze task. These behavioral findings were matched by LPS-induced axonal injury in the CA1 region of the middle dorsal hippocampus (HP), reduction in the size of the HP and the number of neurons in the CA1 region of the middle dorsal HP, and loss of tyrosine hydroxylase immunoreactivity in neurons in the substantia nigra and ventral tegmental areas. Treatment with PBN provided long-lasting protection against the LPS-induced axonal injury and neuronal loss, and improved the associated neurological dysfunctions in juvenile rats.