Deferoxamine reduces intracerebral hemorrhage-induced white matter damage in aged rats.
Deferoxamine reduces intracerebral hemorrhage-induced white matter damage in aged rats.
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DOI：
10.1016/j.expneurol.2015.02.035
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发表时间：
2015-10
影响因子：
5.3
通讯作者：
Hua Y
中科院分区：
文献类型：
--
作者：
Ni W;Okauchi M;Hatakeyama T;Gu Y;Keep RF;Xi G;Hua Y
铁促进幼年大鼠c-Jun N-末端激酶（JNK）活化和脑出血（ICH）后仔猪白色物质损伤。在本研究中，我们研究了去铁胺对ICH诱导的白色物质损伤和JNK激活的影响。雄性Fischer 344大鼠（18月龄）尾内注射100 µ l自体血液或针头插入（假手术）。采用不同的给药方案（剂量、持续时间和时间窗）分别给予去铁胺或溶媒。检测白色物质损伤和JNK活化。我们发现DFX的剂量应大于10 mg/kg，治疗持续时间超过2天，治疗时间窗为12小时，以减少2个月时ICH诱导的白色丢失。ICH诱导的白色物质损伤与JNK激活有关。磷酸化JNK（P-JNK）蛋白水平在脑出血后第1天即开始上调，随后逐渐下降。P-JNK免疫反应主要位于白色束。DFX处理可减少ICH诱导的JNK活化。本研究表明，DFX可以减少ICH诱导的JNK激活和白色物质损伤。
Iron contributes to c-Jun N-terminal kinases (JNK) activation in young rats and white matter injury in piglets after intracerebral hemorrhage (ICH). In the present study, we examined the effect of deferoxamine on ICH-induced white matter injury and JNK activation and in aged rats. Male Fischer 344 rats (18 months old) had either an intracaudate injection of 100 µl of autologous blood or a needle insertion (sham). The rats were treated with deferoxamine or vehicle with different regimen (dosage, duration and time window). White matter injury and activation of JNK were examined. We found that a dose of DFX should at more than 10 mg/kg for a therapeutic duration more than 2 days with a therapeutic time window of 12 hours to reduce ICH-induced white matter loss at 2 months. ICH-induced white matter injury was associated with JNK activation. The protein levels of phosphorylated-JNK (P-JNK) were upregulated at day-1 after ICH and then gradually decreased. P-JNK immunoreactivity was mostly located in white matter bundles. ICH-induced JNK activation was reduced by DFX treatment. This study demonstrated that DFX can reduce ICH-induced JNK activation and white matter damage.