Effect of minocycline on inflammation-induced damage to the blood-brain barrier and white matter during development.
Effect of minocycline on inflammation-induced damage to the blood-brain barrier and white matter during development.
复制标题
米诺环素对发育过程中炎症引起的血脑屏障和白质损伤的影响。
DOI：
10.1111/j.1460-9568.2007.05973.x
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Saunders,NR
中科院分区：
文献类型：
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作者：
Stolp,HB;Ek,CJ;Johansson,PA;Dziegielewska,KM;Potter,AM;Habgood,MD;Saunders,NR
一些暴露于宫内感染的早产儿的白质损伤被认为与血脑屏障的破坏有关。二甲胺四环素是一种据报道可减少炎症引起的脑损伤的药物，我们研究了二甲胺四环素对炎症引起的血脑屏障破坏和白质损伤的影响。有袋负鼠（Monodelphis domestica）的大脑发育主要发生在出生后，因此对其进行了研究。出生后第35天(P)单次腹腔注射脂多糖（LPS） （0.2 mg/kg）加或不加二甲胺四环素（45 mg/kg）可导致血浆蛋白的短期屏障破坏，但对14c -蔗糖没有作用。到P44时，血脑屏障完整性完好，但白质体积减少。在长时间炎症后的P44 (5 × 0.2 mg/kg LPS，间隔48 h)，在脑白质中观察到血液中的蛋白质，后脑对14c -蔗糖的通透性增加了31%。外囊体积和髓磷脂比例分别为对照组的70%和57%。在长期炎症期间给予二甲胺四环素可以恢复血脑屏障的完整性，但不能恢复LPS诱导的白质损伤。这些数据表明，血脑屏障通透性的长期变化仅发生在发育期间长时间的炎症之后；然而，即使是短暂的脑屏障破坏也会对白质造成损害。控制炎症反应可能对预防某些发育性神经系统疾病有影响。
Damage to white matter in some premature infants exposed to intrauterine infections is thought to involve disruption of the blood–brain barrier. We have examined the effect of minocycline, an agent reported to reduce brain damage resulting from inflammation, on inflammation‐induced disruption of the blood–brain barrier and damage to white matter. Post‐natal marsupial opossums (Monodelphis domestica) were studied as most brain development in this species occurs after birth. Single intraperitoneal lipopolysaccharide (LPS) injection (0.2 mg/kg) with or without minocycline (45 mg/kg) at post‐natal day (P)35 caused short‐lasting barrier breakdown to plasma proteins but not to14C‐sucrose. By P44, blood–brain barrier integrity was intact but a reduced volume of white matter was present. At P44 after prolonged inflammation (5 × 0.2 mg/kg LPS at 48 h intervals), proteins from blood were observed within brain white matter and permeability to14C‐sucrose in the hindbrain increased by 31%. The volume of the external capsule and the proportion of myelin were 70 and 57%, respectively, of those in control animals. Minocycline administered during prolonged inflammation restored blood–brain barrier integrity but not LPS‐induced damage to white matter. These data suggest that long‐term changes in blood–brain barrier permeability occur only after a prolonged period of inflammation during development; however, damage to white matter can result from even a short‐lasting breakdown of the barrier. Manipulation of the inflammatory response may have implications for prevention of some developmentally induced neurological conditions.