Thiamine/vitamin B1 deficiency can lead to behavioral changes and neurotoxicity in humans. This may due in part to vascular damage, neuroinflammation and neuronal degeneration in the diencephalon, which is seen in animal models of pyrithiamine-enhanced thiamine deficiency. However, the time course of the progression of these changes in the animal models has been poorly characterized. Therefore, in this study, the progression of: 1) activated microglial association with vasculature; 2) neurodegeneration; and 3) any vascular leakage in the forebrain during the progress of thiamine deficiency were determined. A thiamine deficient diet along with 0.25 mg/kg/d of pyrithiamine was used as the mouse model. Vasculature was identified with Cd31 and microglia with Cd11b and Iba1 immunoreactivity. Neurodegeneration was determined by FJc labeling. The first sign of activated microglia within the thalamic nuclei were detected after 8 d of thiamine deficiency, and by 9 d activated microglia associated primarily with vasculature were clearly present but only in thalamus. At the 8 d time point neurodegeneration was not present in thalamus. However at 9 d, the first signs of neurodegeneration (FJc + neurons) were seen in most animals. Over 80% of the microglia were activated at 10 d but almost exclusively in the thalamus and the number of degenerating neurons was less than 10% of the activated microglia. At 10 d, there were sporadic minor changes in IgG presence in thalamus indicating minor vascular leakage. Dizocilpine (0.2-0.4 mg/kg) or phenobarbital (10-20 mg/kg) was administered to groups of mice from day 8 through day 10 to block neurodegeneration but neither did. In summary, activated microglia start to surround vasculature 1-2 d prior to the start of neurodegeneration. This response may be a means of controlling or repairing vascular damage and leakage. Glutamate excitotoxicity and vascular leakage likely only play a minor role in the early neurodegeneration resulting from thiamine deficiency. However, failure of dysfunctional vasculature endothelium to supply sufficient nutrients to neurons could be contributing to the neurodegeneration.

中文翻译：

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与硫胺素缺乏引起的早期丘脑神经变性有关的小胶质细胞活化和血管反应。

硫胺素/维生素B1缺乏会导致人类行为改变和神经毒性。这可能部分是由于间脑中的血管损伤，神经发炎和神经元变性所致，这在除虫菊酯增强的硫胺素缺乏症的动物模型中可见。但是，这些变化在动物模型中的进展的时程已被不好地描述。因此，在这项研究中，研究进展：1）激活了小胶质细胞与脉管系统的结合；2）神经变性；3）确定硫胺素缺乏症进展过程中前脑中是否有血管渗漏。缺乏硫胺素的饮食和0.25 mg / kg / d的巯乙胺作为小鼠模型。用Cd31鉴定脉管系统，用Cd11b和Iba1免疫反应鉴定小胶质细胞。神经变性通过FJc标记确定。硫胺素缺乏8天后，丘脑核内发现了活化的小胶质细胞的第一个迹象，到9天，主要与脉管系统有关的活化的小胶质细胞明显存在，但仅在丘脑中存在。在第8天的时间点，丘脑中不存在神经变性。然而，在第9天，大多数动物都出现了神经退行性变的最初迹象（FJc +神经元）。超过80％的小胶质细胞在10 d时被激活，但几乎完全在丘脑中，并且退化神经元的数量少于激活的小胶质细胞的10％。在第10天，丘脑中的IgG存在零星的微小变化，表明轻微的血管渗漏。从第8天到第10天，将二唑西平（0.2-0.4 mg / kg）或苯巴比妥（10-20 mg / kg）给予各组小鼠，以阻断神经退行性变，但两者均没有。总之，激活的小胶质细胞在神经变性开始前1-2天开始围绕脉管系统。该反应可以是控制或修复血管损伤和渗漏的手段。谷氨酸兴奋性毒性和血管渗漏可能仅在硫胺素缺乏引起的早期神经变性中起次要作用。然而，功能失调的血管内皮不能为神经元提供足够的营养可能是导致神经变性的原因。