Two components of blood‐brain barrier disruption in the rat

Abstract

1. Permeability of pial venular capillaries to Lucifer Yellow (PLY) was measured using the single microvessel occlusion technique. 2. PLY was extremely low, when measured shortly after the removal of the meninges, consistent with an intact blood-brain barrier, but rose spontaneously to (1·65 ± 0·60) ² 10¦É cm s¢ (mean ± s.d.) within 20-60 min. This first phase of spontaneous disruption lasted 44-164 min. A second phase started when PLY rose sharply, and was characterized by rapid permeability fluctuations with a mean of (12·31 ± 15·14) ² 10¦É cm s¢. 3. The first phase could be mimicked by applying the divalent cation ionophore A23187 in the presence of Ca¥, when PLY rose by (1·47 ± 0·25) ² 10¦É cm s¢ (mean ± s.e.m.). Application of histamine (10 ìÒ) to tight vessels increased PLY by (2·41 ± 0·22) ² 10¦É cm s¢. 4. Substances that raised intraendothelial cAMP of vessels during the first phase of disruption reduced PLY to the initial blood-brain barrier level. 5. The second phase could be prevented by applying catalase. Similar high and fluctuating PLY values could be produced reversibly by applying arachidonic acid or NHÚCl. 6. This is the first report of two distinct types of permeability increase in the cerebral microvasculature, and reasons for this are discussed.

Arachidonic acid increases cerebral microvascular permeability by free radicals in single pial microvessels of the anaesthetized rat

“…Application of 1 mÒ oleic had no permeability-increasing effect. Rapid changes in permeability (as previously reported by Easton, Sarker & Fraser, 1997) were found to be related to the concentration of arachidonic acid ( Fig. 1B and C).…”

“…We found that focally administered arachidonic acid dose-dependently and reversibly increased pial venular capillary permeability to Lucifer Yellow, and that these increases could be very large, consistent with the formation of cerebral oedema. Previously, a high permeability state that had been induced by craniotomy (Easton et al 1997), and in which free radical generation had been implicated, showed a characteristic flickering, not seen at lower permeabilities. As arachidonic acid, in the present series of experiments, also often resulted in a flickering permeability response, not limited to high permeabilities, the idea of free radical formation was raised.…”

“…This evidence favours peroxidation by extracellular free radicals as the crucial step in the permeability response. We previously found that alkalization of the cell interior by ammonium chloride results in a large immediate flickering permeability increase (Easton et al 1997), and this could underlie the way in which free radicals lead to the acute permeability response. It is possible that lipid peroxidation leads to activation of the Na¤-H¤ antiporter, and the resulting pH rise may be the signal that increases permeability.…”

Quantification of transient increase of the blood–brain barrier permeability to macromolecules by optimized focused ultrasound combined with microbubbles

“…Most of the microvessels chosen were post-capillary venules of 15-40 μm diameter for the permeability measurement, and around 1/4 of the microvessels were capillaries. 24,35 The reasons that we currently only measured the permeability of post-capillary venules and capillaries were: 1) to avoid the influence of smooth muscle cells at arteries, arterioles, and large venules, which would contract under stimuli and affect the permeability measurement; 35 2) our previous studies on the BBB permeability were also conducted on this type of post-capillary venules. 23,24 The permeability was determined off-line from the pre-collected images by using ImageJ (National Institutes of Health, Bethesda, MD, USA).…”

“…Postcapillary venules and capillaries were suggested to be more suitable for permeability study since they are relatively less contractible or expandable under stimulations. 35 These properties are necessary for accurate determination of the BBB permeability under FUS stimulations. 35 Finally, their method can only give a relative permeability index, not the true solute permeability for a microvessel defined by the KedemKatchalsky equation.…”