Attenuation of hematoma size and neurological injury with curcumin following intracerebral hemorrhage in mice

被引:52
作者
King, Melanie D. [1 ]
McCracken, D. Jay [1 ]
Wade, F. Marlene [2 ]
Meiler, Steffen E. [2 ]
Alleyne, Cargill H., Jr. [1 ]
Dhandapani, Krishnan M. [1 ]
机构
[1] Georgia Hlth Sci Univ, Dept Neurosurg, Augusta, GA 30809 USA
[2] Georgia Hlth Sci Univ, Dept Anesthesiol & Perioperat Med, Augusta, GA 30809 USA
基金
美国国家卫生研究院;
关键词
hemorrhagic stroke; vasogenic edema; blood-brain barrier; hematoma; mouse; vascular disorders; NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; TRAUMATIC BRAIN-INJURY; GROWTH-FACTOR-BETA; BARRIER BREAKDOWN; VASOGENIC EDEMA; TRIAL; INTERLEUKIN-1-BETA; INFLAMMATION; ACTIVATION;
D O I
10.3171/2011.2.JNS10784
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Object. Intracerebral hemorrhage (ICH) is associated with significant morbidity and mortality. Acute hematoma enlargement is an important predictor of neurological injury and poor clinical prognosis; but 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, the authors investigated whether the curry spice curcumin limited neurovascular injury following ICH in mice. Methods. Intracerebral hemorrhage was induced in adult male CD-1 mice by 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. Results. Curcumin increased hematoma resolution at 72 hours post-ICH. This effect was associated with a significant reduction in the expression of the proinflammatory mediators, tumor necrosis factor a, interleukin-6, and interleukin-1 beta. Curcumin also reduced disruption of the blood-brain barrier and attenuated the formation of vasogenic edema following ICH. Consistent with the reduction in neuroinfiammation and neurovascular injury, curcumin significantly improved neurological outcome scores after ICH. Conclusions. 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. (DOI: 10.3171/2011.2.JNS10784)
引用
收藏
页码:116 / 123
页数:8
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