Early changes in blood‐brain barrier permeability after porto‐caval shunt and liver ischaemia

Abstract

The brain oedema, distribution space (DS) and brain uptake index (BUI), of L-glucose, inulin, B12 vitamin and of three polypeptidic hormones of increasing molecular weight (angiotensin-I, gastrin and insulin) were measured in the rat after sham operation, porto-caval shunt (PCS) or liver ischaemia. At an early stage following PCS or liver ischaemia brain oedema was not constant, and was only demonstrable after liver ischaemia in a large number of animals. Substances without an active transport and with a low diffusion coefficient such as L-glucose and inulin had a very low BUI, unchanged even if the 3H2O brain content or the DS were modified. B12 vitamin, DS and BUI were very high and did not change after liver ischaemia or PCS. Insulin DS and BUI were low in the three groups of animals, whereas it decreased after PCS for gastrin. A significant increase of BUI and DS (without any cerebral oedema) was demonstrated for angiotensin-I, a polypeptidic hormone of molecular weight 1300. This polypeptidic marker is in the same range of MW as the preliminary recently recognized medium-sized molecules which may be involved in the pathogenesis of encephalopathy during experimental acute liver failure. However, not only the MW, but the nature of such polypeptides may be of importance in the genesis of this limited impairment of BBB permeability.

Hepatic encephalopathy in cirrhotic and portacaval shunted dogs: Lack of changes in brain GABA uptake, brain GABA levels, brain glutamic acid decarboxylase activity and brain postsynaptic GABA receptors

“…Nonselective increases in BBB permeability have been repeatedly reported in animal models of fulminant hepatic failure (16,17) and are probably related to structural changes in the BBB induced by brain edema in this experimental model (18). In contrast, studies in animals with PCS demonstrated a selective increase in the transport of large neutral amino acids (19) without physical breakdown of the BBB (20). In our model, the BBB appeared to be unaltered as shown by the absence of changes in sucrose uptake and the impermeability of trypan blue.…”

Brain Quinolinic Acid in Chronic Experimental Hepatic Encephalopathy: Effects of an Exogenous Ammonium Acetate Challenge

“…This hypothesis is supported by the increased hepatic TDO activity and the unaltered brain indoleamine-2,3-dioxygenase (the enzyme involved in extrahepatic QUIN production) activity recently reported in acute experimental liver failure (Basile et al, 1995b) . Furthermore, an abnormal BBB permeability has been reported in acute experimental liver failure (Livingstone et al, 1977;Crinquette et al ., 1982 ;Horowitz et al, 1983 ;Zaki et al, 1984) . It is interesting that QUIN in itself has the ability to affect BBB permeability, for example, by facilitation of the penetration of magnesium into brain tissue (Rothe et al, 1993) .…”

Alterations of Blood Brain Barrier Function in Hyperammonemia: An Overview

“…Hepatic encephalopathy evoked by PCA was demonstrated to be associated with decreased brain glucose use and energy metabolism (DeJoseph and Hawkins 1991), and a similar effect was noted in rats with TAA-induced HE (Hilgier et al 1991). Brain uptake index of glucose was reduced after PCA in rats (Sarna et al 1979; Crinquette et al 1982) and this decrease was almost entirely due to the decrease in plasma glucose concentrations (Mans et al 1986). GLUT-1, the principal glucose transporter at the BBB responsible for supplying CNS cells with blood-borne glucose was demonstrated to be induced by ALF (Bélanger et al 2006).…”