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Region-selective permeability of the blood-brain barrier to α-aminoisobutyric acid during thiamine deficiency and following its reversal
Metabolic Brain Disease ( IF 3.2 ) Pub Date : 2020-11-27 , DOI: 10.1007/s11011-020-00644-w
Alan S Hazell 1 , Roger F Butterworth 1
Affiliation  

Thiamine deficiency (TD) results in focal lesions in several regions of the rat brain including the thalamus and inferior colliculus. Since alterations in blood-brain barrier (BBB) integrity may play a role in this damage, we have examined the influence of TD on the unidirectional blood-to-brain transfer constant (Ki) of the low molecular weight species α-aminoisobutyric acid (AIB) in vulnerable and non-vulnerable brain regions at different stages during progression of the disorder, and following its reversal with thiamine. Analysis of the regional distribution of Ki values showed early (day 10) increased transfer of [14C]-AIB across the BBB in the vulnerable medial thalamus as well as the non-vulnerable caudate and hippocampus. At the acute symptomatic stage (day 14), more widespread BBB permeability changes were detected in most areas including the lateral thalamus, inferior colliculus, and non-vulnerable cerebellum and pons. Twenty-four hours following thiamine replenishment, a heterogeneous pattern of increased BBB permeability was observed in which many structures maintained increased uptake of [14C]-AIB. No increase in the [3H]-dextran space, a marker of intravascular volume, was detected in brain regions during the progress of TD, suggesting that BBB permeability to this large tracer was unaffected. These results indicate that BBB opening i) occurs early during TD, ii) is not restricted to vulnerable areas of the brain, iii) is progressive, iv) persists for at least 24 h following treatment with thiamine, and v) is likely selective in nature, depending on the molecular species being transported.



中文翻译:

硫胺素缺乏期间血脑屏障对 α-氨基异丁酸的区域选择性渗透性及其逆转

硫胺素缺乏 (TD) 会导致大鼠大脑多个区域的局灶性病变,包括丘脑和下丘。由于血脑屏障 (BBB) 完整性的改变可能在这种损伤中起作用,我们研究了 TD 对低分子量物质 α-氨基异丁酸的单向血脑转移常数 (K i ) 的影响(AIB)在疾病进展期间的不同阶段的脆弱和非脆弱大脑区域中,并在其被硫胺素逆转之后。对 K i值区域分布的分析表明,早期(第 10 天)[ 14C]-AIB 穿过脆弱的内侧丘脑以及非脆弱的尾状核和海马中的 BBB。在急性症状阶段(第 14 天),在大多数区域检测到更广泛的 BBB 通透性变化,包括外侧丘脑、下丘、非脆弱小脑和脑桥。补充硫胺素后 24 小时,观察到 BBB 渗透性增加的异质模式,其中许多结构保持 [ 14 C]-AIB吸收增加。[ 3H]-葡聚糖空间是血管内容量的标志物,在 TD 过程中在大脑区域中检测到,表明 BBB 对这种大示踪剂的渗透性不受影响。这些结果表明 BBB 开放 i) 在 TD 早期发生,ii) 不限于大脑的脆弱区域,iii) 是渐进的,iv) 在用硫胺素治疗后持续至少 24 小时,并且 v) 可能在性质,取决于被运输的分子种类。

更新日期:2021-01-18
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