Resistance to 3-mercaptopropionic acid-induced seizures in hepatic encephalopathy.
Sleutelwoorden
Abstract
OBJECTIVE
To determine if a model of hepatic encephalopathy (HE) exhibits decreased sensitivity to the neuronal effects of a drug that induces seizures as a consequence of decreasing GABA-mediated inhibitory neurotransmission.
METHODS
3-Mercaptopropionic Acid (MPA) is an inhibitor of L-glutamate decarboxylase which catalyzes the synthesis of GABA from glutamate. MPA was administered, either by intraperitoneal or intracerebroventricular injection, into rats with stage III HE due to thioacetamide-induced fulminant hepatic failure and into normal control rats.
RESULTS
When MPA was administered by intraperitoneal injection, seizure-inducing doses were similar for rats with HE and control rats. However, when a constant dose of MPA (330 micrograms) was administered by intracerebroventricular injection, rats with HE took significantly longer to develop seizures than control rats (16.2 vs. 7.3 minutes; p < 0.0005).
CONCLUSIONS
In a model of HE: (i) There is increased resistance to the convulsive effects of MPA; and (ii) This phenomenon is apparent when MPA is given centrally, but not when it is given peripherally. Increased resistance to the development of a complication of reduced GABA-mediated neurotransmission induced by MPA in the model provides support for the hypothesis that HE is associated with increased GABA-mediated inhibitory neurotransmission.
