Novel molecular imaging of cell death in experimental cerebral stroke
Novel molecular imaging of cell death in experimental cerebral stroke
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DOI：
10.1016/j.brainres.2007.01.095
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发表时间：
2007-05-04
期刊：
影响因子：
2.9
通讯作者：
Ziv, Ilan
中科院分区：
文献类型：
--
作者：
Reshef, Ayelet;Shirvan, Anat;Ziv, Ilan
细胞死亡是脑缺血的基本神经病理基础，其无创性成像有助于提高卒中患者的诊断和治疗水平。ApoSense是一类新的低分子化合物家族，用于体内细胞死亡的检测和成像。我们现在报道在啮齿动物实验性卒中中，通过静脉注射ApoSense化合物DDC(双丹西司汀)，对细胞死亡的成像和神经保护治疗的有效性的监测。采用大鼠和小鼠大脑中动脉(MCA)短期或永久性闭塞模型，分别注射DDC或H-3标记的DDC。分别进行了体外荧光和放射自显影研究，包括评估梗死区DDC摄取与组织病理学的相关性。用半胱氨酸天冬氨酸氨基转移酶抑制剂(Q-VD-OPH)诱导神经保护作用，并用DDC监测其作用。静脉注射DDC后，DDC选择性地聚集在梗死区受损神经元中。抑制半胱氨酸天冬氨酸氨基转移酶可使脑梗塞体积缩小45%，DDC对此有很好的报道。这是首次报道用小分子探针在体检测脑卒中细胞死亡。DDC可能有助于解决目前的“神经影像/神经组织学鸿沟”，用于中风相关细胞死亡程度的分子评估。(C)2007 Elsevier B.V.保留所有权利。
Cell death is the basic neuropathological substrate in cerebral ischemia, and its non-invasive imaging may improve diagnosis and treatment for stroke patients. ApoSense is a novel family of low-molecular weight compounds for detection and imaging of cell death in vivo. We now report on imaging of cell death and monitoring of efficacy of neuroprotective treatment in vivo by intravenous administration of the ApoSense compound DDC (didansylcystine), in experimental stroke in rodents. Rats and mice were subjected to a short-term (2 h) or permanent occlusion of the middle cerebral artery (MCA) and injected with DDC or H-3-labeled DDC. Fluorescent and autoradiographic studies, respectively, were performed ex vivo, comprising assessment of DDC uptake in the infarct region, in correlation with tissue histopathology. Neuroprotection was induced by a caspase inhibitor (Q-VD-OPH), and its effect was monitored by DDC. Following its intravenous administration, DDC accumulated selectively in injured neurons within the region of infarct. Caspase inhibition exerted a 45% reduction in infarct volume, which was well reported by DDC. This is the first report on a small molecule probe for detection in vivo of cell death in cerebral stroke. DDC may potentially assist in addressing the current "neuroimaging/neurohistology gap", for molecular assessment of the extent of stroke-related cell death. (c) 2007 Elsevier B.V. All rights reserved.