急性和延迟去铁胺治疗可减轻新生大鼠脑室内出血后的长期后遗症。
Acute and delayed deferoxamine treatment attenuates long-term sequelae after germinal matrix hemorrhage in neonatal rats.
机构信息
From the Department of Physiology and Pharmacology, Loma Linda University School of Medicine, CA.
出版信息
Stroke. 2014 Aug;45(8):2475-9. doi: 10.1161/STROKEAHA.114.005079. Epub 2014 Jun 19.
BACKGROUND AND PURPOSE
This study investigated if acute and delayed deferoxamine treatment attenuates long-term sequelae after germinal matrix hemorrhage (GMH).
METHODS
Bacterial collagenase (0.3 U) was infused intraparenchymally into the right hemispheric ganglionic eminence in P7 rat pups to induce GMH. GMH animals received either deferoxamine or vehicle twice a day for 7 consecutive days. Deferoxamine administration was initiated at either 1 hour or 72 hours post-GMH. Long-term neurocognitive deficits and motor coordination were assessed using Morris water maze, rotarod, and foot fault tests between day 21 to 28 post-GMH. At 28 days post-GMH, brain morphology was assessed and extracellular matrix protein (fibronectin and vitronectin) expression was determined.
RESULTS
Acute and delayed deferoxamine treatment improved long-term motor and cognitive function at 21 to 28 days post-GMH. Attenuated neurofunction was paralleled with improved overall brain morphology at 28 days post-GMH, reducing white matter loss, basal ganglia loss, posthemorrhagic ventricular dilation, and cortical loss. GMH resulted in significantly increased expression of fibronectin and vitronectin, which was reversed by acute and delayed deferoxamine treatment.
CONCLUSIONS
Acute and delayed deferoxamine administration ameliorated long-term sequelae after GMH.
背景与目的
本研究旨在探讨急性和延迟使用去铁胺治疗是否能减轻脑室内出血（GMH）后的长期后遗症。
方法
在 P7 日龄大鼠幼仔的右侧神经节隆起内脑实质内注入细菌胶原酶（0.3 U）以诱导 GMH。GMH 动物每天接受去铁胺或载体两次，连续 7 天。去铁胺给药在 GMH 后 1 小时或 72 小时开始。GMH 后 21 至 28 天，通过 Morris 水迷宫、转棒和足误试验评估长期神经认知缺陷和运动协调能力。GMH 后 28 天，评估脑形态并确定细胞外基质蛋白（纤维连接蛋白和 vitronectin）的表达。
结果
急性和延迟去铁胺治疗可改善 GMH 后 21 至 28 天的长期运动和认知功能。改善的神经功能与 GMH 后 28 天的整体脑形态改善相平行，减少了白质损失、基底节损失、出血后脑室扩张和皮质损失。GMH 导致纤维连接蛋白和 vitronectin 的表达显著增加，急性和延迟去铁胺治疗可逆转这种增加。
结论
急性和延迟去铁胺给药可改善 GMH 后的长期后遗症。
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