Attenuation of hematoma size and neurological injury with curcumin following intracerebral hemorrhage in mice.
Attenuation of hematoma size and neurological injury with curcumin following intracerebral hemorrhage in mice.
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DOI：
10.3171/2011.2.jns10784
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发表时间：
2011-07
影响因子：
4.1
通讯作者：
Dhandapani KM
中科院分区：
文献类型：
--
作者：
King MD;McCracken DJ;Wade FM;Meiler SE;Alleyne CH Jr;Dhandapani KM
脑出血（ICH）与显著的患者发病率和死亡率相关。急性血肿扩大是神经系统损伤和临床预后不良的重要预测因素;然而，神经外科凝块清除术可能并非对所有患者都可行，治疗选择在很大程度上仍然是支持性的。因此，需要新的治疗方法来促进血肿消退。在本研究中，我们调查了咖喱香料，姜黄素，是否限制了小鼠脑出血后的神经血管损伤。通过脑内注射胶原酶或自体血在成年雄性CD-1小鼠中诱导ICH。在ICH后6小时内给予临床相关剂量的姜黄素（75-300 mg/kg），并在前72小时内评估血肿体积、炎症基因表达、血脑屏障通透性和脑水肿。进行神经学评估，以将神经血管保护与功能结局相关联。在ICH后72小时，姜黄素增加血肿消退。该效应与促炎介质、肿瘤坏死因子-α、白细胞介素-6和白细胞介素-1 β的表达显著降低相关。姜黄素还减少了对血脑屏障的破坏，并减弱了ICH后血管源性水肿的形成。与神经炎症和神经血管损伤的减少一致，姜黄素显著改善了ICH后的神经结局评分。姜黄素促进血肿消退，并限制ICH后的神经损伤。这些数据可能表明姜黄素作为辅助治疗的临床效用，以减少脑损伤和改善患者的预后。
Intracerebral hemorrhage (ICH) is associated with significant patient morbidity and mortality. Acute hematoma enlargement is an important predictor of neurological injury and poor clinical prognosis; however, neurosurgical clot evacuation may not be feasible in all patients and treatment options remain largely supportive. Thus, novel therapeutic approaches to promote hematoma resolution are needed. In the present study, we investigated whether the curry spice, curcumin, limited neurovascular injury following ICH in mice. ICH was induced in adult male CD-1 mice by the intracerebral administration of collagenase or autologous blood. Clinically-relevant doses of curcumin (75–300 mg/kg) were administered up to 6 hours after ICH and hematoma volume, inflammatory gene expression, blood-brain barrier permeability, and brain edema were assessed over the first 72 hours. Neurological assessments were performed to correlate neurovascular protection with functional outcomes. Curcumin increased hematoma resolution at 72 hours post-ICH. This effect was associated with a significant reduction in the expression of the pro-inflammatory mediators, tumor necrosis factor-α, interleukin-6, and interleukin-1β. Curcumin also reduced disruption of the blood-brain barrier and attenuated the formation of vasogenic edema following ICH. Consistent with the reduction in neuroinflammation and neurovascular injury, curcumin significantly improved neurological outcome scores after ICH. Curcumin promoted hematoma resolution and limited neurological injury following ICH. These data may indicate clinical utility for curcumin as an adjunct therapy to reduce brain injury and improve patient outcome.