Permeability of blood‐brain and blood‐nerve barriers in experimental diabetes mellitus in the anaesthetized rat

Abstract

SUMMARYDiabetes was induced with streptozotocin in rats weighing about 160 g. These were maintained with age-matched controls for up to 14 months, blood glucose being periodically monitored. Half the diabetic and control rats received the aldose reductase inhibitor, Ponalrestat, in their diet. At 3 weeks, 6-7 months and 13-14 months, the vascular permeability in regions of brain, and in optic and sciatic nerves, were measured by maintaining radiotracers in the bloodstream -'l25-albumin (100 min), [14C]sucrose (60 min) and 1311-albumin (5 min) -followed by tissue sampling and counting at termination. 131I-albumin estimated residual intravascular plasma.Diabetes of up to 13-14 weeks caused no measurable increase in the sucrose permeability of microvessels in eight different brain regions, in optic or in sciatic nerve. At 3 weeks of diabetes, sucrose permeability in all brain regions and in optic nerve was reduced relative to that in controls. Extravascular albumin entry into different regions of brain and optic nerve was insignificant and insensitive to diabetes, except in the hypothalamus and optic nerves where it was raised with increasing duration of diabetes. In sciatic nerve, extravascular albumin distribution was markedly increased by diabetes, but sucrose permeability was not demonstrably affected. At the level used in the diet, Ponalrestat reduced the sorbitol content of diabetic sciatic nerve but did not protect again the increased permeability to albumin.

Glutamate permeability at the blood-brain barrier in insulinopenic and insulin-resistant rats

“…The human study suggests such might not be the case. Indeed, in rats treated with STZ, though some reports indicate physical BBB disruption can occur as early as 14-28 days after STZ injection for small molecules like sucrose (12,32), other studies offer data providing little indication of BBB disruption (for mannitol or sucrose) in rats treated with STZ as long as 9 or 14 months earlier (33,34). It seems that diabetes affects the BBB differently for different molecules (35).…”

Decreased blood–brain barrier permeability to fluorescein in streptozotocin-treated rats

“…However, the specific effects of diabetes on the blood-brain barrier (BBB) remain controversial. Studies utilizing the streptozotocin (STZ)-induced model of diabetes to assess its effect on the BBB have indicated that the BBB remains intact [4], whereas recent work [29] indicates that BBB permeability is increased in STZ diabetes. Clinical studies of BBB function in diabetes have been similarly disparate [7,38].…”

Tight junction protein expression and barrier properties of immortalized mouse brain microvessel endothelial cells

“…These endothelial cells are distinguishable from other endothelial cell beds by a number of characteristics; they have very low levels of transcellular endocytosis, express specific ion and peptide transporters in a polarized manner, and form a low permeability physical barrier between the blood and the brain due to the presence of tight junctions between adjacent endothelial cells [34,63,74]. The barrier function of the BBB can be disrupted by a number of different stimuli or pathophysiologies, including hyperosmolar-induced cell shrinkage [22,92], hypoxic stress and stroke [5,23,98], Alzheimer's disease [70,88], diabetes [13,19], multiple sclerosis [58,111] and inflammatory pain [20,65].…”