Pfefferbaum Adolf, Adalsteinsson Elfar, Bell Richard L, Sullivan Edith V
Neuroscience Program, SRI International, Menlo Park, CA, USA.
Neuropsychopharmacology. 2007 May;32(5):1159-77. doi: 10.1038/sj.npp.1301107. Epub 2006 May 24.
Wernicke's encephalopathy (WE) is characterized by lesions in thalamus, hypothalamus (including mammillary nuclei), and inferior colliculi, results in serious disabilities, has an etiology of thiamine deficiency, is treatable with thiamine, and occurs most commonly with alcoholism. Despite decades of study, whether alcohol exposure exacerbates the neuropathology or retards its resolution remains controversial. To examine patterns of brain damage and recovery resulting from thiamine deprivation with and without alcohol exposure, we conducted in vivo magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) at 3 T in alcohol-preferring (P) rats, which had voluntarily consumed large amounts of alcohol before thiamine manipulation. A total of 18 adult male P rats (nine alcohol-exposed) received a thiamine-deficient diet for 2 weeks: 10 (five alcohol-exposed) received intraperitoneal (i.p.) pyrithiamine (PT) and eight (four alcohol-exposed) received i.p. thiamine supplementation. Neurological signs developed by day 14. Rats were scanned before thiamine depletion and 18 and 35 days after thiamine repletion. Two-dimensional J-resolved MRS single-voxel spectra with water reference were collected in a voxel subtending the thalamus; metabolite quantification was corrected for voxel tissue content. MRI identified significant enlargement of dorsal ventricles and increase in signal intensities in thalamus, inferior colliculi, and mammillary nuclei of PT compared with thiamine-treated (TT) groups from MRI 1-2, followed by significant normalization from MRI 2-3 in thalamus and colliculi, but not mammillary nuclei and lateral ventricles. Voxel-by-voxel analysis revealed additional hyperintense signal clusters in the dorsal and ventral hippocampus and enlargement of the fourth ventricle. MRS showed a significant decline and then partial recovery in thalamic N-acetylaspartate, a marker of neuronal integrity, in PT compared with TT rats, with no change detected in creatine, choline, or glutamate. PT rats with prior alcohol exposure exhibited attenuated recovery in the thalamus and arrested growth of the corpus callosum; further, two of the five alcohol-exposed PT rats died prematurely. Parenchymal and ventricular changes with thiamine manipulation concur with human radiological signs of WE. The enduring macrostructural and neurochemical abnormalities involving critical nodes of Papez circuit carry liabilities for development of amnesia and incomplete recovery from other cognitive and motor functions subserved by the affected neural systems.
韦尼克脑病（WE）的特征是丘脑、下丘脑（包括乳头体核）和下丘出现病变，会导致严重残疾，其病因是硫胺素缺乏，可用硫胺素治疗，最常见于酒精中毒患者。尽管经过了数十年的研究，但酒精暴露是会加剧神经病理学变化还是会延缓其恢复，仍存在争议。为了研究在有或没有酒精暴露的情况下硫胺素缺乏所导致的脑损伤和恢复模式，我们对偏好酒精的（P）大鼠进行了3T的体内磁共振成像（MRI）和磁共振波谱（MRS）检查，这些大鼠在硫胺素处理前自愿摄入了大量酒精。总共18只成年雄性P大鼠（9只暴露于酒精）接受了为期2周的硫胺素缺乏饮食：10只（5只暴露于酒精）接受腹腔注射（i.p.）吡硫胺（PT），8只（4只暴露于酒精）接受腹腔注射硫胺素补充。在第14天出现了神经症状。在硫胺素耗竭前以及硫胺素补充后18天和35天对大鼠进行扫描。在一个覆盖丘脑的体素中收集了以水为参考的二维J分辨MRS单体素光谱；代谢物定量针对体素组织含量进行了校正。MRI显示，与硫胺素治疗（TT）组相比，PT组的背侧脑室明显扩大，丘脑、下丘和乳头体核的信号强度增加，从MRI 1 - 2开始，随后丘脑和下丘在MRI 2 - 3时有明显的正常化，但乳头体核和侧脑室没有。逐体素分析显示，背侧和腹侧海马体还有额外的高强度信号簇，以及第四脑室扩大。MRS显示，与TT大鼠相比，PT大鼠丘脑神经元完整性标志物N - 乙酰天门冬氨酸显著下降，然后部分恢复，肌酸、胆碱或谷氨酸未检测到变化。先前暴露于酒精的PT大鼠丘脑恢复减弱，胼胝体生长停滞；此外，5只暴露于酒精的PT大鼠中有2只过早死亡。硫胺素处理引起的实质和脑室变化与人类WE的放射学征象一致。涉及帕佩兹回路关键节点的持久宏观结构和神经化学异常会导致失忆以及受影响神经系统所支持的其他认知和运动功能无法完全恢复。
