Blood-brain barrier permeability for ammonia in patients with different grades of liver fibrosis is not different from healthy controls.
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Blood-brain barrier permeability for ammonia in patients with different grades of liver fibrosis is not different from healthy controls. / Goldbecker, Annemarie; Buchert, Ralph; Berding, Georg; Bokemeyer, Martin; Lichtinghagen, Ralf; Wilke, Florian; Ahl, Björn; Weissenborn, Karin.
In: J CEREBR BLOOD F MET, Vol. 30, No. 7, 7, 2010, p. 1384-1393.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Blood-brain barrier permeability for ammonia in patients with different grades of liver fibrosis is not different from healthy controls.
AU - Goldbecker, Annemarie
AU - Buchert, Ralph
AU - Berding, Georg
AU - Bokemeyer, Martin
AU - Lichtinghagen, Ralf
AU - Wilke, Florian
AU - Ahl, Björn
AU - Weissenborn, Karin
PY - 2010
Y1 - 2010
N2 - Increased blood-brain barrier (BBB) permeability for ammonia is considered to be an integral part of the pathophysiology of hepatic encephalopathy (HE) in patients with liver cirrhosis. Increased glutamate-/glutamine-signal intensity in magnetic resonance spectroscopic studies of the brain in cirrhotic patients was explained as a consequence of increased cerebral ammonia uptake. As similar spectroscopic alterations are present in patients with liver fibrosis, we hypothesized that BBB permeability for ammonia is already increased in liver fibrosis, and thereby contributing to the development of HE. To test this hypothesis, cerebral perfusion and ammonia metabolism were examined through positron emission tomography with (15)O-water, respectively, (13)N-ammonia in patients with Ishak grades 2 and 4 fibrosis, cirrhosis, and healthy controls. There were neither global nor regional differences of cerebral blood flow, the rate constant of unidirectional transport of ammonia from blood into brain tissue, the permeability surface area product of the BBB for ammonia, the net metabolic clearance rate constant of ammonia from blood into glutamine in brain, or the metabolic rate of ammonia. The hypothesis that increased permeability of the BBB for ammonia in patients with liver fibrosis contributes to the later development of HE could not be supported by this study.
AB - Increased blood-brain barrier (BBB) permeability for ammonia is considered to be an integral part of the pathophysiology of hepatic encephalopathy (HE) in patients with liver cirrhosis. Increased glutamate-/glutamine-signal intensity in magnetic resonance spectroscopic studies of the brain in cirrhotic patients was explained as a consequence of increased cerebral ammonia uptake. As similar spectroscopic alterations are present in patients with liver fibrosis, we hypothesized that BBB permeability for ammonia is already increased in liver fibrosis, and thereby contributing to the development of HE. To test this hypothesis, cerebral perfusion and ammonia metabolism were examined through positron emission tomography with (15)O-water, respectively, (13)N-ammonia in patients with Ishak grades 2 and 4 fibrosis, cirrhosis, and healthy controls. There were neither global nor regional differences of cerebral blood flow, the rate constant of unidirectional transport of ammonia from blood into brain tissue, the permeability surface area product of the BBB for ammonia, the net metabolic clearance rate constant of ammonia from blood into glutamine in brain, or the metabolic rate of ammonia. The hypothesis that increased permeability of the BBB for ammonia in patients with liver fibrosis contributes to the later development of HE could not be supported by this study.
KW - Humans
KW - Aged
KW - Female
KW - Middle Aged
KW - Positron-Emission Tomography methods
KW - Ammonia metabolism
KW - Blood-Brain Barrier metabolism
KW - Brain blood supply
KW - Capillary Permeability physiology
KW - Glutamine metabolism
KW - Hepatic Encephalopathy etiology
KW - Liver Cirrhosis complications
KW - Magnetic Resonance Spectroscopy
KW - Humans
KW - Aged
KW - Female
KW - Middle Aged
KW - Positron-Emission Tomography methods
KW - Ammonia metabolism
KW - Blood-Brain Barrier metabolism
KW - Brain blood supply
KW - Capillary Permeability physiology
KW - Glutamine metabolism
KW - Hepatic Encephalopathy etiology
KW - Liver Cirrhosis complications
KW - Magnetic Resonance Spectroscopy
M3 - SCORING: Zeitschriftenaufsatz
VL - 30
SP - 1384
EP - 1393
JO - J CEREBR BLOOD F MET
JF - J CEREBR BLOOD F MET
SN - 0271-678X
IS - 7
M1 - 7
ER -
