Sears E S, McCandless D W, Chandler M D
J Neurosci Res. 1985;14(2):255-61. doi: 10.1002/jnr.490140210.
Both hyperammonemia and blood-brain barrier (BBB) breakdown have been implicated in the evolution of hepatic encephalopathy. To define a possible relationship, Swiss Albino mice were subjected to sublethal encephalopathic doses of ammonium acetate; the integrity of the BBB was determined grossly with Evans blue and quantitatively with [14C]-alpha-aminoisobutyrate (AIB). Some animals were injected with a dose of ammonium acetate sufficient to maintain coma for 1 hr (AC group). One group, termed stuporous (AS), received only enough ammonium acetate to interfere with grooming and exploratory activity; this dosage was insufficient to completely block the righting response, which was absent in the AC group. When compared to that of controls (CON) receiving normal saline instead of ammonium acetate, cerebral tissue from the AC group was stained blue and contained nearly double the amount of AIB; AS group brain tissue was unstained and the AIB content did not differ significantly from normal. Some of the AC group were pretreated with drugs known to retard BBB breakdown; one set received dexamethasone (AC-DXMN), another the ornithine decarboxylase inhibitor difluoromethyl ornithine (AC-DFMO), and a third L-ornithine (AC-ORN). Brain tissue from the AC-ORN group stained blue and AIB content did not differ significantly from that of the untreated AC group. Cerebral tissue of the AC-DXMN pretreatment group stained light blue; AIB content was significantly lower than in the AC group and greater than the CON group. The AC-DFMO brains were unstained and AIB content was significantly lower than in the AC group but did not differ significantly from CON. These results indicate that hyperammonemia may induce BBB breakdown but that the disruption of barrier integrity is not antecedent to the development of coma, although it seems to coincide with coma in time.(ABSTRACT TRUNCATED AT 250 WORDS)
高氨血症和血脑屏障（BBB）破坏均与肝性脑病的进展有关。为确定二者之间的可能关系，对瑞士白化小鼠给予亚致死性剂量的醋酸铵以诱发肝性脑病；通过伊文思蓝大体观察血脑屏障的完整性，并用[14C] -α-氨基异丁酸（AIB）进行定量测定。部分动物注射足以维持1小时昏迷状态的醋酸铵剂量（AC组）。另一组称为昏睡组（AS），仅给予足以干扰梳理和探索活动的醋酸铵剂量；该剂量不足以完全阻断翻正反射，而AC组则无此反射。与接受生理盐水而非醋酸铵的对照组（CON）相比，AC组脑组织被染成蓝色，且AIB含量几乎翻倍；AS组脑组织未被染色，AIB含量与正常组无显著差异。部分AC组动物预先用已知可延缓血脑屏障破坏的药物进行处理；一组接受地塞米松（AC-DXMN），另一组接受鸟氨酸脱羧酶抑制剂二氟甲基鸟氨酸（AC-DFMO），第三组接受L-鸟氨酸（AC-ORN）。AC-ORN组脑组织被染成蓝色，AIB含量与未处理的AC组无显著差异。AC-DXMN预处理组脑组织染成浅蓝色；AIB含量显著低于AC组，但高于CON组。AC-DFMO组脑组织未被染色，AIB含量显著低于AC组，但与CON组无显著差异。这些结果表明，高氨血症可能诱导血脑屏障破坏，但屏障完整性的破坏并非昏迷发生的先决条件，尽管它似乎与昏迷同时出现。（摘要截选至250词）
