Blocking NMDA Receptors Delays Death in Rats with Acute Liver Failure by Dual Protective Mechanisms in Kidney and Brain
PBN-AR
Instytucja
Instytut Medycyny Doświadczalnej i Klinicznej im. Mirosława Mossakowskiego Polskiej Akademii Nauk
Źródłowe zdarzenia ewaluacyjne
Informacje podstawowe
Główny język publikacji
en
Czasopismo
NeuroMolecular Medicine
ISSN
1535-1084
EISSN
1559-1174
Wydawca
HUMANA PRESS INC
DOI
URL
Rok publikacji
2014
Numer zeszytu
2
Strony od-do
360-375
Numer tomu
16
Identyfikator DOI
Liczba arkuszy
1,85
Słowa kluczowe
en
Hyperammonemia
Acute liver failure
NMDA receptor
Intracranial pressure
Blood flow
Tubular injury
Glomerular filtration rate
Streszczenia
Język
en
Treść
Treatment of patients with acute liver failure (ALF) is unsatisfactory and mortality remains unacceptably high. Blocking NMDA receptors delays or prevents death of rats with ALF. The underlying mechanisms remain unclear. Clarifying these mechanisms will help to design more efficient treatments to increase patient's survival. The aim of this work was to shed light on the mechanisms by which blocking NMDA receptors delays rat's death in ALF. ALF was induced by galactosamine injection. NMDA receptors were blocked by continuous MK-801 administration. Edema and cerebral blood flow were assessed by magnetic resonance. The time course of ammonia levels in brain, muscle, blood, and urine; of glutamine, lactate, and water content in brain; of glomerular filtration rate and kidney damage; and of hepatic encephalopathy (HE) and intracranial pressure was assessed. ALF reduces kidney glomerular filtration rate (GFR) as reflected by reduced inulin clearance. GFR reduction is due to both reduced renal perfusion and kidney tubular damage as reflected by increased Kim-1 in urine and histological analysis. Blocking NMDA receptors delays kidney damage, allowing transient increased GFR and ammonia elimination which delays hyperammonemia and associated changes in brain. Blocking NMDA receptors does not prevent cerebral edema or blood-brain barrier permeability but reduces or prevents changes in cerebral blood flow and brain lactate. The data show that dual protective effects of MK-801 in kidney and brain delay cerebral alterations, HE, intracranial pressure increase and death. NMDA receptors antagonists may increase survival of patients with ALF by providing additional time for liver transplantation or regeneration.
Cechy publikacji
ORIGINAL_ARTICLE
Inne
System-identifier
590434
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