Imaging experimental cerebral malaria in vivo:: Significant role of ischemic brain edema
Imaging experimental cerebral malaria in vivo:: Significant role of ischemic brain edema
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DOI：
10.1523/jneurosci.1002-05.2005
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发表时间：
2005-08-10
影响因子：
5.3
通讯作者：
Cozzone, PJ
中科院分区：
文献类型：
--
作者：
Penet, MF;Viola, A;Cozzone, PJ
第一次在体内的实验性脑型疟疾的磁共振研究。脑部受累是疟疾的致命并发症。为了探索感染伯氏疟原虫ANKA的易感小鼠的脑，应用多模式磁共振技术（成像、扩散、灌注、血管造影、波谱学）。它们揭示了血管损伤，包括血脑屏障破坏和炎症过程引起的血管损伤。我们提供了脑型疟疾血脑屏障破坏的第一个体内演示。检测到严重水肿形成以及脑灌注减少，并伴有缺血性代谢特征，高能磷酸盐减少和脑乳酸升高。此外，血管造影术为主要血流动力学功能障碍提供了令人信服的证据。实际上，水肿通过压迫脑动脉进一步加剧缺血，随后导致血流崩溃，最终导致死亡。这些发现表明炎性和缺血性病变的共存，并证明水肿在实验性脑型疟疾的致命结局中的优势作用。它们提高了我们对脑型疟疾发病机制的理解，并可能为治疗的定量监测提供必要的非侵入性替代标记物。
The first in vivo magnetic resonance study of experimental cerebral malaria is presented. Cerebral involvement is a lethal complication of malaria. To explore the brain of susceptible mice infected with Plasmodium berghei ANKA, multimodal magnetic resonance techniques were applied (imaging, diffusion, perfusion, angiography, spectroscopy). They reveal vascular damage including blood-brain barrier disruption and hemorrhages attributable to inflammatory processes. We provide the first in vivo demonstration for blood-brain barrier breakdown in cerebral malaria. Major edema formation as well as reduced brain perfusion was detected and is accompanied by an ischemic metabolic profile with reduction of high-energy phosphates and elevated brain lactate. In addition, angiography supplies compelling evidence for major hemodynamics dysfunction. Actually, edema further worsens ischemia by compressing cerebral arteries, which subsequently leads to a collapse of the blood flow that ultimately represents the cause of death. These findings demonstrate the coexistence of inflammatory and ischemic lesions and prove the preponderant role of edema in the fatal outcome of experimental cerebral malaria. They improve our understanding of the pathogenesis of cerebral malaria and may provide the necessary noninvasive surrogate markers for quantitative monitoring of treatment.