Behavioural and histopathological alterations in mice with cerebral malaria
Behavioural and histopathological alterations in mice with cerebral malaria
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DOI：
10.1111/j.1365-2990.2006.00706.x
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发表时间：
2006-04-01
影响因子：
5
通讯作者：
Schmutzhard, E
中科院分区：
文献类型：
--
作者：
Lackner, P;Beer, R;Schmutzhard, E
应用SHIRPA方案的初步筛选，研究了小鼠脑型疟疾（CM）和无脑型疟疾（non-CM）的感觉运动功能和行为的不同特征。对不同脑区进行组织学分析，并分析出血和血细胞堵塞脑血管的相对大小。与对照动物相比，患有CM的动物在疾病的进展过程中出现广泛的行为和功能改变，在死亡前36小时评估的所有功能类别中均出现统计学显著性损伤。大脑表型的早期功能指标是反射和感觉系统以及神经精神状态的损害。功能恶化通过组织病理学变化的程度来证实，CM动物的SHIRPA评分与脑出血的平均大小之间存在统计学显著相关性。此外，图像分析显示，与其他感兴趣的区域相比，前脑和脑干中脑病变的相对面积明显更大。我们的研究结果表明，评估的感觉和运动任务的SHIRPA初级屏幕是适当的早期在体内歧视的大脑参与实验鼠疟疾。我们的研究结果还表明，脑实质出血所指示的功能障碍的程度和脑病变的大小之间的相关性。将SHIRPA方案应用于患有CM的动物的功能表征可能有助于新抗疟疾和潜在神经保护疗法的临床前评估。
Different features of sensorimotor function and behaviour were studied in murine cerebral malaria (CM) and malaria without cerebral involvement (non-CM) applying the primary screen of the SHIRPA protocol. Histopathological analysis of distinct brain regions was performed and the relative size of haemorrhages and plugging of blood cells to brain vasculature was analysed. Animals suffering from CM develop a wide range of behavioural and functional alterations in the progressive course of the disease with a statistically significant impairment in all functional categories assessed 36 h prior to death when compared with control animals. Early functional indicators of cerebral phenotype are impairments in reflex and sensory system and in neuropsychiatric state. Deterioration in function is paralleled by the degree of histopathological changes with a statistically significant correlation between the SHIRPA score of CM animals and the mean size of brain haemorrhage. Furthermore, image analysis yielded that the relative area of the brain lesions was significantly larger in the forebrain and brainstem compared with the other regions of interest. Our results indicate that assessment of sensory and motor tasks by the SHIRPA primary screen is appropriate for the early in vivo discrimination of cerebral involvement in experimental murine malaria. Our findings also suggest a correlation between the degree of functional impairment and the size of the brain lesions as indicated by parenchymal haemorrhage. Applying the SHIRPA protocol in the functional characterization of animals suffering from CM might prove useful in the preclinical assessment of new antimalarial and potential neuroprotective therapies.