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)