STUDIES OF RELATING TO THE PATHOGENESIS OF HEPATIC ENCEPHALOPATHY

家兔视觉诱发反应（VERs）的异常模式 暴发性肝衰竭（FHF）引起的肝性脑病（HE） 类似于巴比妥酸盐引起的昏迷， 苯并二氮杂卓或产量-氨基-丁酸（GABA）激动剂。 因为这些 药物通过与神经元上的结合位点相互作用来诱导神经抑制， GABA受体复合物的突触后神经膜，这些发现 表明HE中神经元活动的模式可能类似于 与GABA抑制性神经递质系统的激活有关。 在中枢神经系统外，GABA的主要来源是肠道细菌， 肝脏是它的催化剂。 当在家兔中诱导FHF时， 在HE的出现之前，血浆GABA水平增加， 血脑屏障（BBB）通透性的非特异性增加 一种非代谢的GABA异构体 考虑到快速的 GABA的代谢是一种改良的Oldendorf技术， 已经被用来证明大脑摄取 GABA本身的指数在HE中增加。 FHF与 脑内受体密度显著增加， 抑制性氨基酸神经递质和苯二氮卓类（BZ）， 脑内受体密度显著降低， 兴奋性氨基酸神经递质，并与变化， 神经膜的组成。 GABA受体拮抗剂和BZ 受体拮抗剂诱导FHF所致HE的改善， 临床和电生理（VER模式）。 这些发现 表明在急性肝衰竭中：（i）血浆GABA能够进入 脑通过可渗透的BBB;（ii）脑可能对 兴奋性氨基酸神经递质和更敏感的抑制 氨基酸神经递质和BZ，和（iii）内源性BZ配体 可能通过增强GABA能紧张性参与HE的神经抑制。

The abnormal pattern of visual evoked responses (VERs) in rabbits with hepatic encephalopathy (HE) due to fulminant hepatic failure (FHF) resembles that associated with coma induced by a barbiturate, a benzodiazepine or a yield-amino-butyric acid (GABA) agonist. As these drugs induce neural inhibition by interacting with binding sites on the GABA receptor complex on postsynaptic neural membranes, these findings suggest that the pattern of neuronal activity in HE may resemble that associated with activation of the GABA inhibitory neurotransmitter system. Outside the CNS the main source of GABA is gut bacteria and the main site of its catabolism is the liver. When FHF was induced in rabbits the onset of HE was preceded by an increase in the plasma levels of GABA and by a nonspecific increase in the permeability of the blood brain barrier (BBB) to a nonmetabolized isomer of GABA. To take account of the rapid metabolism of GABA a modified Oldendorf technique, which employed the use of a vascular marker, has been used to demonstrate that the brain uptake index for GABA itself is increases in HE. FHF was associated with significant increased in the densities of brain receptors for the inhibitory amino acid neurotransmitters, and for benzodiazepines (BZ), with significant decreases in the densities of brain receptors for the excitatory amino acid neurotransmitters, and with changes in the composition of neural membranes. Both a GABA receptor antagonist and a BZ receptor antagonist induced an amelioration of HE due to FHF both clinically and electrophysiologically (VER pattern). These findings suggest that in acute liver failure: (i) plasma GABA gains access to the brain through a permeable BBB; (ii) the brain may be less sensitive to excitatory amino acid neurotransmitters and more sensitive to inhibitory amino acid neurotransmitters and to BZ and (iii) an endogenous BZ ligand may contribute to the neural inhibition of HE by augmenting GABAergic tone.