A magnetic resonance imaging study of early brain injury in a rat model of acute DFP intoxication.
A magnetic resonance imaging study of early brain injury in a rat model of acute DFP intoxication.
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DOI：
10.1016/j.neuro.2017.11.009
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发表时间：
2018-05
期刊：
影响因子：
3.4
通讯作者：
Garbow JR
中科院分区：
文献类型：
--
作者：
Hobson BA;Rowland DJ;Supasai S;Harvey DJ;Lein PJ;Garbow JR
目前对由有机磷引起的癫痫发作的治疗不能充分预防进行性神经变性或延迟性认知障碍。开发更有效的治疗方法一直具有挑战性，因为这些延迟后果的发病机制尚不明确。使用磁共振成像（MRI），我们之前报道了在OP，二异丙基氟磷酸盐（DFP）急性中毒大鼠模型中持续数月的脑损伤。然而，这些病变的早期时空进展尚不清楚。为了解决这一数据缺口，我们使用体内MRI在急性DFP中毒后的头3天纵向监测脑损伤。分别于DFP （4 mg/kg, sc）急性中毒后6、12、18、24、48、72 h对成年雄性Sprague Dawley大鼠进行MR成像，并用FluoroJade C （FJC）染色对其脑组织进行相关组织学检查，评估神经退行性。急性DFP中毒引起中度至重度癫痫发作。t2加权（T2w）解剖成像显示丘脑、梨状皮质、大脑皮质、海马、纹状体和黑质内明显病变，与神经变性相关，可见FJC阳性细胞带。病变严重程度的半定量评估显示，损伤的发生和进展存在显著的区域差异，提示异氟醚麻醉可能调节病变严重程度。这些结果表明，减轻OP中毒后脑损伤的治疗干预时间可能是区域依赖的，MRI对OP引起的损伤的纵向评估可能是评估治疗反应的有力工具。
Current treatments for seizures induced by organophosphates do not protect sufficiently against progressive neurodegeneration or delayed cognitive impairment. Developing more effective therapeutic approaches has been challenging because the pathogenesis of these delayed consequences is poorly defined. Using magnetic resonance imaging (MRI), we previously reported brain lesions that persist for months in a rat model of acute intoxication with the OP, diisopropylfluorophosphate (DFP). However, the early spatiotemporal progression of these lesions remains unknown. To address this data gap, we used in vivo MRI to longitudinally monitor brain lesions during the first 3 d following acute DFP intoxication. Adult male Sprague Dawley rats acutely intoxicated with DFP (4 mg/kg, sc) were MR imaged at 6, 12, 18, 24, 48, 72 h post-DFP, and their brains then taken for correlative histology to assess neurodegeneration using FluoroJade C (FJC) staining. Acute DFP intoxication elicited moderate-to-severe seizure activity. T2-weighted (T2w) anatomic imaging revealed prominent lesions within the thalamus, piriform cortex, cerebral cortex, hippocampus, corpus striatum, and substantia nigra that corresponded to neurodegeneration, evident as bands of FJC positive cells. Semi-quantitative assessment of lesion severity demonstrated significant regional variation in the onset and progression of injury, and suggested that lesion severity may be modulated by isoflurane anesthesia. These results imply that the timing of therapeutic intervention for attenuating brain injury following OP intoxication may be regionally dependent, and that longitudinal assessment of OP-induced damage by MRI may be a powerful tool for assessing therapeutic response.
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影响因子：
6.1
作者：
Duffy BA;Chun KP;Ma D;Lythgoe MF;Scott RC
通讯作者：
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