Department of Neurosurgery, R5018 Biomedical Science, Research Building, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.
Stroke. 2011 Dec;42(12):3587-93. doi: 10.1161/STROKEAHA.111.623926. Epub 2011 Oct 13.
Brain iron overload plays a detrimental role in brain injury after intracerebral hemorrhage (ICH). A recent study found that minocycline acts as an iron chelator and reduces iron-induced neuronal death in vitro. The present study investigated if minocycline reduces iron overload after ICH and iron-induced brain injury in vivo.
This study was divided into 4 parts: (1) rats with different sizes of ICH were euthanized 3 days later for serum total iron and brain edema determination; (2) rats had an ICH treated with minocycline or vehicle. Serum iron, brain iron, and brain iron handling proteins were measured; (3) rats had an intracaudate injection of saline, iron, iron+minocycline, or iron+macrophage/microglia inhibitory factor and were used for brain edema and neuronal death measurements; and (4) rats had an intracaudate injection of iron and were treated with minocycline. The brains were used for edema measurement.
After ICH, serum total iron and brain nonheme iron increased and these changes were reduced by minocycline treatment. Minocycline also reduced ICH-induced upregulation of brain iron handling proteins and neuronal death. Intracaudate injection of iron caused brain edema, blood-brain barrier leakage, and brain cell death, all of which were significantly reduced by coinjection with minocycline.
The current study found that minocycline reduces iron overload after ICH and iron-induced brain injury. It is also well known minocycline is an inhibitor of microglial activation. Minocycline may be very useful for patients with ICH because both iron accumulation and microglia activation contribute to brain damage after ICH.
脑铁过载在脑出血（ICH）后脑损伤中起有害作用。最近的一项研究发现米诺环素作为一种铁螯合剂，可减少体外铁诱导的神经元死亡。本研究探讨了米诺环素是否能减少 ICH 后铁过载和体内铁诱导的脑损伤。
本研究分为 4 部分：（1）不同大小 ICH 的大鼠在 3 天后安乐死，用于测定血清总铁和脑水肿；（2）ICH 大鼠用米诺环素或载体治疗。测定血清铁、脑铁和脑铁处理蛋白；（3）大鼠尾状核内注射生理盐水、铁、铁+米诺环素或铁+巨噬细胞/小胶质细胞抑制因子，用于脑水肿和神经元死亡测量；（4）大鼠尾状核内注射铁并用米诺环素治疗。脑用于测量脑水肿。
ICH 后，血清总铁和脑非血红素铁增加，米诺环素治疗可减少这些变化。米诺环素还可降低 ICH 诱导的脑铁处理蛋白上调和神经元死亡。尾状核内注射铁可引起脑水肿、血脑屏障渗漏和脑细胞死亡，米诺环素共注射可显著减轻这些损伤。
本研究发现米诺环素可减少 ICH 后铁过载和铁诱导的脑损伤。众所周知，米诺环素是小胶质细胞激活的抑制剂。米诺环素对 ICH 患者可能非常有用，因为铁积累和小胶质细胞激活都有助于 ICH 后的脑损伤。
