Acute Ammonia Intoxication-Induced Seizures but not Ammonia Per Se Contribute to the Electrophysiological Changes in Rat Brain

Abstract

Background and Aim: Hepatic encephalopathy (HE) is a major complication in patients with mild to severe liver disease. HE is characterized by confusion, inverted sleep-wake cycles, disorientation, behavioral changes, impaired cognition, and motor disturbances, as well as increased brain edema and intracranial pressure. The molecular basis for these changes in HE remains unclear. Elevated blood and brain ammonia levels have been strongly implicated in its pathogenesis. Whether ammonia play any role in electrophysiological changes in HE that may be involved in neurobehavioral, biochemical and molecular changes observed in HE was examined. Methods: Male Wister albino rats were injected (i.p) with ammonium acetate (500 and 800 mg/kg) and liver toxin acetaminophen (AMPN, 500 mg/kg). Results: The AACE-treated group developed seizures within 10 min and survived post-treatment without any additional seizure incident. However, more than 70% of AMPN treated animals died after 56 hours. Hippocampal slices were prepared from these animals (1 hr after AACE and 40 h after AMPN, pre-coma stage) and electrophysiological changes were measured. A paired-pulse facilitation (PPF) sequence in which stimulation pulse pairs were delivered at intervals of 20-480 ms and the filed excitatory postsynaptic potential (EPSP) slope were calculated. A depressed PPF was observed in slices from both AACE and AMPN treated animals. Further, inhibition of seizures in AACE group showed reversal of these electrophysiological changes, while these inhibitors failed to prevent electrophysiological changes induced by AMPN. Additionally, seizure inducing agent's picrotoxin (PCT) and pentylenetetrazol (PTZ) showed electrophysiological changes similar to AACE, and that inhibition of PCT and PTZ induced seizures reversed electrophysiological changes. Conclusion: These findings suggest that the effect of acute ammonia intoxication on electrophysiological changes may be due to the effect of ammonia-induced seizures, but not due to ammonia per se. The author have none to declare.