From the Department of Neurosurgery, University of Michigan, Ann Arbor (M.W., Y.H., R.F.K., S.W., N.N., G.X.).
Department of Neurosurgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China (M.W.).
Stroke. 2019 Jul;50(7):1859-1868. doi: 10.1161/STROKEAHA.119.025170. Epub 2019 Jun 10.
Background and Purpose- Early erythrolysis in the hematoma contributes to brain injury after intracerebral hemorrhage (ICH). This study investigated the effects of N-acetylheparin, a complement inhibitor, and aurin tricarboxylic acid, a membrane attack complex inhibitor, on early erythrolysis, brain iron deposition, and brain injury in aged rats. Methods- There were 3 parts in the study. First, aged (18 months old) male Fischer 344 rats had an ICH. The time course of erythrolysis in the hematoma was determined by T2* weighted magnetic resonance imaging, and the expression of CD163 was examined. Second, aged rats had an ICH with N-acetylheparin or vehicle. Rats were euthanized at days 1, 3, and 28 after magnetic resonance imaging (T2-, T2*-weighted, and T2* array) and behavioral tests. Brains were used for immunohistochemistry. Third, aged rats had an ICH with avaurin tricarboxylic acid or vehicle. The rats had magnetic resonance imaging and behavioral tests and were euthanized at day 3. Brains were used for immunohistochemistry. Results- Early erythrolysis occurred within the clot in aged F344 rats. There were increased numbers of CD163-positive cells after ICH. Almost all perihematomal CD163-positive cells were microglia/macrophages, while positive neurons were found more distant from the hematoma. Coinjection of N-acetylheparin attenuated erythrolysis, iron accumulation, CD163 expression, microglia activation, brain swelling, and neuronal death in the acute phase, as well as reducing brain atrophy and neurological deficits in the chronic phase. Coinjection of aurin tricarboxylic acid also reduced erythrolysis and ICH-induced brain injury. Conclusions- Inhibiting complement activation resulted in less erythrolysis and brain injury after ICH.
背景与目的-脑出血（ICH）后早期血肿内红细胞溶解可导致脑损伤。本研究旨在探讨补体抑制剂乙酰肝素和膜攻击复合物抑制剂三羧酸对老年大鼠早期红细胞溶解、脑铁沉积和脑损伤的影响。方法-本研究分为 3 部分。首先，对 18 月龄雄性 Fischer 344 大鼠行 ICH 造模。采用 T2加权磁共振成像（MRI）测定血肿内红细胞溶解的时间过程，并检测 CD163 的表达。其次，对 ICH 大鼠行乙酰肝素或载体治疗。在 MRI（T2-、T2-加权和 T2*阵列）和行为学测试后第 1、3 和 28 天处死大鼠，取脑进行免疫组化。第三，对 ICH 大鼠行三羧酸或载体治疗。MRI 和行为学测试后第 3 天处死大鼠，取脑进行免疫组化。结果-老年 F344 大鼠血肿内发生早期红细胞溶解，ICH 后 CD163 阳性细胞增多。血肿周围的 CD163 阳性细胞几乎均为小胶质细胞/巨噬细胞，而远离血肿的阳性神经元则较少。乙酰肝素共注射可减轻急性期红细胞溶解、铁积累、CD163 表达、小胶质细胞激活、脑水肿和神经元死亡，慢性期还可减轻脑萎缩和神经功能缺损。三羧酸共注射也可减少红细胞溶解和 ICH 诱导的脑损伤。结论-抑制补体激活可减少 ICH 后红细胞溶解和脑损伤。
