Increased blood-brain transfer in a rabbit model of acute liver failure.
Increased blood-brain transfer in a rabbit model of acute liver failure.
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DOI：
10.5555/uri:pii:0016508583902032
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发表时间：
1983
期刊：
影响因子：
29.4
通讯作者：
M. Horowitz;D. Schafer;P. Molnar;E. Jones;R. Blasberg;C. Patlak;J. Waggoner;J. Fenstermacher
中科院分区：
文献类型：
--
作者：
M. Horowitz;D. Schafer;P. Molnar;E. Jones;R. Blasberg;C. Patlak;J. Waggoner;J. Fenstermacher
用定量放射自显影法研究了正常家兔和选择性肝毒素半乳糖胺致急性肝衰竭家兔血脑转移[14C] α -氨基异丁酸。半乳糖胺注射后2和7小时，α -氨基异丁酸在对照动物和动物体内的血脑转移量相似，但在半乳糖胺治疗后11和18小时，α -氨基异丁酸在动物大脑某些灰质区域的转移量增加了5至10倍。在对照组和治疗组之间，白质对[14C] α -氨基异丁酸的摄取没有可检测到的差异。灰质区域α -氨基异丁酸转移的增加表明这些区域发生了脑毛细血管通透性的普遍或非特异性增加。除半乳糖胺后18 h组1只外，其余各组均未见早期肝性脑病的临床症状。因此，α -氨基异丁酸的血脑转移增强先于显性肝性脑病的发展。静脉注射[14C]半乳糖胺后的放射性分布表明，几乎没有肝毒素局限于大脑，这表明药物本身对血脑屏障或大脑没有直接影响。在11和18 h时α -氨基异丁酸的摄取增加意味着其他溶质的转移也会增强，中枢神经系统的稳态会受到损害，由此导致的脑液成分的变化可能有助于或引起肝性脑病。
The blood-to-brain transfer of [14C]alpha-aminoisobutyric acid was investigated by quantitative autoradiography in normal rabbits and rabbits with acute liver failure induced by the selective hepatotoxin galactosamine. The blood-to-brain transfer of alpha-aminoisobutyric acid was similar in control animals and animals 2 and 7 h after galactosamine injections, but was increased five- to tenfold in certain gray-matter areas of the brain in animals 11 and 18 h after galactosamine treatment. No detectable differences in white-matter uptake of [14C]alpha-aminoisobutyric acid were found between the control and treated groups. The increase in alpha-aminoisobutyric acid transfer within the gray-matter areas suggested that a general or nonspecific increase in brain capillary permeability occurred in these areas. No clinical signs of early hepatic encephalopathy were observed in the treated rabbits, except for 1 animal from the 18-h postgalactosamine group. Thus, enhanced blood-brain transfer of alpha-aminoisobutyric acid preceded the development of overt hepatic encephalopathy. The distribution of radioactivity after the intravenous administration of [14C]galactosamine showed that virtually none of the hepatotoxin localized in the brain, suggesting that the drug itself does not have a direct effect upon the blood-brain barrier or the brain. The increased uptake of alpha-aminoisobutyric acid at 11 and 18 h implies that the transfer of other solutes would also be enhanced, that central nervous system homeostasis would be compromised, and that the resulting changes in brain fluid composition could contribute to or cause hepatic encephalopathy.