Brain barrier properties and cerebral blood flow in neonatal mice exposed to cerebral hypoxia-ischemia.
Brain barrier properties and cerebral blood flow in neonatal mice exposed to cerebral hypoxia-ischemia.
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DOI：
10.1038/jcbfm.2014.255
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发表时间：
2015-05
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影响因子：
--
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对发育中的大脑的侮辱通常会导致无法弥补的损害，从而导致运动和认知功能的长期缺陷。目前，新生儿缺氧缺血性脑病 (HIE) 的唯一治疗方法是低温治疗，但其临床益处有限。我们研究了 HIE 新生儿模型中血脑屏障 (BBB) 和局部脑血流量 (rCBF) 的变化，以进一步了解潜在的病理机制。九天大的小鼠幼崽的大脑大致相当于近期人类胎儿的大脑，它们受到缺氧缺血的影响。缺氧缺血在损伤后数小时内增加了血脑屏障对小分子和大分子的通透性，并在接下来的几天内恢复正常。 BBB 的开放与 BBB 蛋白表达的变化相关，而基因转录水平增加表明对 BBB 的直接分子损伤，但也暗示了补偿机制。脑病理学与缺氧期间 rCBF 的减少以及血脑屏障受损的区域密切相关，表明这些密切相关。损伤后血脑屏障的短暂开放可能会导致病理，但同时也为治疗提供了更好地到达大脑梗塞区域的机会。
Insults to the developing brain often result in irreparable damage resulting in long-term deficits in motor and cognitive functions. The only treatment today for hypoxic-ischemic encephalopathy (HIE) in newborns is hypothermia, which has limited clinical benefit. We have studied changes to the blood–brain barriers (BBB) as well as regional cerebral blood flow (rCBF) in a neonatal model of HIE to further understand the underlying pathologic mechanisms. Nine-day old mice pups, brain roughly equivalent to the near-term human fetus, were subjected to hypoxia-ischemia. Hypoxia-ischemia increased BBB permeability to small and large molecules within hours after the insult, which normalized in the following days. The opening of the BBB was associated with changes to BBB protein expression whereas gene transcript levels were increased showing direct molecular damage to the BBB but also suggesting compensatory mechanisms. Brain pathology was closely related to reductions in rCBF during the hypoxia as well as the areas with compromised BBB showing that these are intimately linked. The transient opening of the BBB after the insult is likely to contribute to the pathology but at the same time provides an opportunity for therapeutics to better reach the infarcted areas in the brain.
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影响因子：
4.2
作者：
D'Angelo, Barbara;Ek, C. Joakim;Mallard, Carina
通讯作者：
Mallard, Carina
DOI：
10.1097/00004647-200001000-00003
发表时间：
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作者：
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通讯作者：
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7.8
作者：
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通讯作者：
Tsukita, S