Depletion of brain histamine produces regionally selective protection against thiamine deficiency-induced lesions in the rat.
Depletion of brain histamine produces regionally selective protection against thiamine deficiency-induced lesions in the rat.
复制标题
脑组胺的消耗可对大鼠体内硫胺素缺乏引起的病变产生区域选择性保护。
DOI：
10.1023/a:1019930206196
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发表时间：
2002
影响因子：
3.6
通讯作者：
Hough,LindsayB
中科院分区：
文献类型：
--
作者：
Langlais,PhilipJ;McRee,RobertCarter;Nalwalk,JuliaA;Hough,LindsayB
血脑屏障的破坏和随后的自由基、乳酸和谷氨酸的积累似乎是硫胺素缺乏(TD)导致丘脑损伤的直接原因。触发这些事件的机制尚不清楚，但最近的证据表明，组胺发挥了重要作用。因此，我们研究了组胺耗竭对吡硫胺诱导的硫胺缺乏(PTD)大鼠丘脑损伤的影响。慢性侧脑室(i.c.v.，7天)注射α-氟甲基组氨酸(FMH)，结合双侧ibotenate破坏结节乳头(TM)核和i.c.v团注中含有组胺的神经元。48/80是一种有效的肥大细胞脱颗粒剂，用来耗尽脑组织胺水平。接受FMH+48/80+TM联合损伤的PTD大鼠比接受静脉注射的PTD大鼠早大约1天出现急性神经症状，包括自发性癫痫发作。注射赋形剂和假病变的TM。在硫胺素恢复1周后进行检查时，PTD载体+假损伤动物在中线、板层内、腹侧、外侧和后侧核有严重的神经元丢失和胶质增生。经FMH+48/80+TM损毁处理的PTD动物，除胶状核和前腹核神经元完全丧失外，丘脑内几乎没有神经元丢失或小胶质细胞增殖的证据。这些数据表明，组胺在韦尼克脑病大鼠模型丘脑损伤的发展过程中具有显著的区域选择性作用。此外，这些数据表明癫痫发作和丘脑损伤之间存在分离，或者组胺在癫痫发作相关的丘脑损伤中起着重要作用。
Breakdown of the blood brain barrier and the subsequent accumulation of free radicals, lactate, and glutamate appear to be the immediate causes of thiamine deficiency (TD)-induced damage to thalamus. The mechanisms triggering these events are unknown but recent evidence suggests an important role of histamine. We therefore studied the effects of histamine depletion on thalamic lesions in the pyrithiamine-induced thiamine deficient (PTD) rat. Chronic intracerebroventricular (i.c.v., 7 days) infusion of α-fluoromethylhistidine (FMH), combined with bilateral ibotenate destruction of the histamine-containing neurons in the tuberomammillary (TM) nucleus and bolus i.c.v. infusion of 48/80, a potent mast cell degranulating agent, was used to deplete brain histamine levels. PTD rats receiving combined FMH + 48/80 + TM lesions developed acute neurological symptoms, including spontaneous seizures, approximately 1 day earlier than PTD rats treated with i.c.v. infusion of vehicle and sham lesions of the TM. When examined 1 week after restoration of thiamine, the PTD vehicle + sham lesion animals contained severe neuronal loss and gliosis in midline, intralaminar, ventral, lateral, and posterior nuclei. PTD animals treated with FMH + 48/80 + TM lesions had little evidence of neuronal loss or microglial proliferation in thalamus except in the gelatinosus and anteroventral nuclei, in which there was complete neuronal loss. These data demonstrate a significant and regionally selective role of histamine in the development of thalamic lesions in a rat model of Wernicke's encephalopathy. Furthermore, these data suggest either a dissociation between seizures and thalamic lesions or a significant role of histamine in seizure-related damage to the thalamus.