Complement Inhibition Attenuates Early Erythrolysis in the Hematoma and Brain Injury in Aged Rats
Complement Inhibition Attenuates Early Erythrolysis in the Hematoma and Brain Injury in Aged Rats
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DOI：
10.1161/strokeaha.119.025170
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发表时间：
2019-07-01
期刊：
影响因子：
8.3
通讯作者：
Xi, Guohua
中科院分区：
文献类型：
--
作者：
Wang, Ming;Hua, Ya;Xi, Guohua
背景和目的--脑出血后早期血肿内红细胞溶解导致脑损伤.本研究探讨了补体抑制剂N-乙酰肝素和膜攻击复合物抑制剂金精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：本研究分为三部分.首先，老年（18月龄）雄性Fischer 344大鼠发生ICH。通过T2* 加权磁共振成像确定血肿中红细胞溶解的时间过程，并检查CD 163的表达。其次，老年大鼠使用N-乙酰肝素或溶剂后出现ICH。在磁共振成像（T2加权、T2* 加权和T2* 阵列）和行为测试后第1、3和28天对大鼠实施安乐死。脑用于免疫组织化学。第三，老年大鼠在使用avaurin三羧酸或溶剂时发生ICH。对大鼠进行磁共振成像和行为测试，并在第3天实施安乐死。脑用于免疫组织化学。结果：F344老年大鼠的血凝块内出现早期红细胞溶解。脑出血后CD 163阳性细胞数量增加。几乎所有血肿周围的CD 163阳性细胞是小胶质细胞/巨噬细胞，而阳性神经元被发现更远离血肿。共注射N-乙酰肝素减弱红细胞溶解，铁积累，CD 163表达，小胶质细胞活化，脑肿胀，神经元死亡在急性期，以及减少脑萎缩和神经功能缺损在慢性期。共注射金精三羧酸也减少红细胞溶解和ICH诱导的脑损伤。结论-抑制补体激活导致ICH后红细胞溶解和脑损伤减少。
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.