Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
PLoS One. 2013 Jul 2;8(7):e67691. doi: 10.1371/journal.pone.0067691. Print 2013.
Intracerebral hemorrhage (ICH) is featured by poor prognosis such as high mortality rate and severe neurological dysfunction. In humans, several valuables including hematoma volume and ventricular expansion of hemorrhage are known to correlate with the extent of mortality and neurological dysfunction. However, relationship between hematoma conditions and the severity of symptoms in animal ICH models has not been clarified. Here we addressed this issue by using 7-tesla magnetic resonance imaging (MRI) on collagenase-induced ICH model in mice. We found that the mortality rate and the performance in behavioral tests did not correlate well with the volume of hematoma. In contrast, when hemorrhage invaded the internal capsule, mice exhibited high mortality and showed poor sensorimotor performance. High mortality rate and poor performance in behavioral tests were also observed when hemorrhage invaded the lateral ventricle, although worsened symptoms associated with ventricular hemorrhage were apparent only during early phase of the disease. These results clearly indicate that invasion of the internal capsule or the lateral ventricle by hematoma is a critical determinant of poor prognosis in experimental ICH model in mice as well as in human ICH patients. MRI assessment may be a powerful tool to refine investigations of pathogenic mechanisms and evaluations of drug effects in animal models of ICH.
脑出血(ICH)的预后较差,死亡率和严重神经功能障碍高。在人类中,已知几个有价值的因素,包括血肿量和出血的脑室扩张,与死亡率和神经功能障碍的严重程度相关。然而,在动物 ICH 模型中,血肿状况与症状严重程度之间的关系尚未阐明。在这里,我们使用 7 特斯拉磁共振成像(MRI)在胶原酶诱导的小鼠 ICH 模型中解决了这个问题。我们发现死亡率和行为测试中的表现与血肿量没有很好的相关性。相比之下,当出血侵犯内囊时,小鼠死亡率高,感觉运动功能差。当出血侵犯侧脑室时,也观察到高死亡率和行为测试表现不佳,尽管与脑室出血相关的症状仅在疾病早期明显恶化。这些结果清楚地表明,血肿对内囊或侧脑室的侵犯是实验性 ICH 模型以及人类 ICH 患者预后不良的关键决定因素。MRI 评估可能是一种强大的工具,可以完善对 ICH 动物模型中发病机制的研究和药物疗效的评估。