Local and global cerebral blood flow and glucose utilization in the alpha-galactosidase A knockout mouse model of Fabry disease.
Local and global cerebral blood flow and glucose utilization in the alpha-galactosidase A knockout mouse model of Fabry disease.
复制标题
法布里病 α-半乳糖苷酶 A 敲除小鼠模型中的局部和整体脑血流量和葡萄糖利用。
DOI：
10.1046/j.1471-4159.2001.00669.x
复制
发表时间：
2001
影响因子：
4.7
通讯作者：
Moore,DF
中科院分区：
文献类型：
--
作者：
Itoh,Y;Esaki,T;Cook,M;Qasba,P;Shimoji,K;Alroy,J;Brady,RO;Sokoloff,L;Moore,DF
Fabry病是一种X连锁的溶酶体疾病，其特征是α-半乳糖苷酶A活性低下，细胞内糖鞘糖脂积聚，主要是球三糖神经酰胺(GB3)。临床上，患者偶尔会出现中枢神经系统功能障碍。为了研究脑功能障碍的病理生理学机制，我们检测了α-半乳糖苷酶A基因敲除小鼠18个脑结构的葡萄糖利用率和脑血流量。在Fabry小鼠中，全局CMRglc在统计学上显著降低了22%(p<； 0.01)。所有18个结构的局部CMRglc下降了14%到33%。间脑、尾壳核、脑干和小脑皮质的所有结构的减少具有统计学意义(p<； 005)。在相同的18个结构中，Fabry组小鼠的整体脑血流量(CBF)和局部脑血流量(CBF)均低于对照组，但无统计学意义。脑组织学检查未发现脑梗塞，但脑血管壁上有丰富的Gb3沉积，神经元沉积定位于延髓。这些结果表明，Fabry鼠的大脑能量代谢受损，但不一定是由于循环不足。
Fabry disease is an X‐linked lysosomal disorder characterized by deficient α‐galactosidase A activity and intracellular accumulations of glycosphingolipids, mainly globotriaosylceramide (Gb3). Clinically, patients occasionally present CNS dysfunction. To examine the pathophysiology underlying brain dysfunction, we examined glucose utilization (CMRglc) and cerebral blood flow (CBF) globally and locally in 18 brain structures in the α‐galactosidase A gene knockout mouse. Global CMRglcwas statistically significantly reduced by 22% in Fabry mice (p< 0.01). All 18 structures showed decreases in local CMRglcranging from 14% to 33%. The decreases in all structures of the diencephalon, caudate‐putamen, brain stem, and cerebellar cortex were statistically significant (p< 0.05). Global cerebral blood flow (CBF) and local CBF measured in the same 18 structures were lower in Fabry mice than in control mice, but none statistically significantly. Histological examination of brain revealed no cerebral infarcts but abundant Gb3 deposits in the walls of the cerebral vessels with neuronal deposits localized to the medulla oblongata. These results indicate an impairment in cerebral energy metabolism in the Fabry mice, but one not necessarily due to circulatory insufficiency.