Molecular, Cellular and Clinical Aspects of Intracerebral Hemorrhage: Are the Enemies Within?
Molecular, Cellular and Clinical Aspects of Intracerebral Hemorrhage: Are the Enemies Within?
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DOI：
10.2174/1570159x14666151230110058
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发表时间：
2016
影响因子：
5.3
通讯作者：
Bozza FA
中科院分区：
文献类型：
--
作者：
Righy C;Bozza MT;Oliveira MF;Bozza FA
出血性脑卒中是一种发病率和死亡率都很高的疾病。除了由出血性卒中引起的肿块病变外，血液衍生产物（BDP）（血红蛋白（Hb）、血红素和铁）等物质可诱导强效炎症反应，并对神经元、星形胶质细胞和小胶质细胞产生直接毒性作用。在本综述中，我们讨论了继发于出血性卒中的脑损伤的机制，重点是参与BDP作为细胞氧化还原失衡，炎症和谷氨酸兴奋性毒性的主要球员。潜在的自然保护机制，对游离血红蛋白和血红素，如触珠蛋白和血红素结合蛋白，分别突出。最后，我们讨论了针对游离铁和血红素清除以及炎症的实验和临床试验，作为潜在的新疗法，以尽量减少出血性中风对大脑结构和功能的破坏性影响。
Hemorrhagic stroke is a disease with high incidence and mortality rates. In addition to the mass lesions that result from hemorrhagic stroke, substances such as the blood-derived products (BDP) (hemoglobin (Hb), heme and iron) induce a potent inflammatory response and exert direct toxic effects on neurons, astrocytes, and microglia. In the present review, we discuss the mechanisms of brain injury secondary to hemorrhagic stroke, focusing on the involvement of BDP as major players of cellular redox imbalance, inflammation, and glutamate excitotoxicity. Potential natural mechanisms of protection against free Hb and heme such as haptoglobin and hemopexin, respectively, are highlighted. We finally discuss the experimental and clinical trials targeting free iron and heme scavenging as well as inflammation, as potential new therapies to minimize the devastating effects of hemorrhagic stroke on brain structure and function.