O2 radicals in arachidonate-induced increased blood-brain barrier permeability to proteins

Abstract

We studied the effect of topical application of arachidonate on the brain surface on blood-brain barrier permeability to either 125I-labeled human albumin or to horseradish peroxidase administered intravenously. Arachidonate was applied under a cranial window, and the concentration of albumin was measured in brain after elimination of the blood by perfusion-fixation. Permeability to 125I-labeled albumin was increased in the superficial 4 mm of the cortex but not in the deeper cortical layer 4-6 mm from the surface. This increased permeability to albumin was prevented by simultaneous topical application of superoxide dismutase (60 U/ml) and catalase (40 U/ml). Alterations in vascular permeability to horseradish peroxidase were evaluated in semiquantitative fashion, and they behaved similarly. Extravasated horseradish peroxidase was found in the wall of penetrating arterioles, and to a lesser extent in the wall of intraparenchymal vessels and capillaries, but not in the wall of pial arterioles or veins, although these latter vessels displayed focal endothelial lesions. We conclude that arachidonate increases the blood-brain barrier permeability to proteins. This increase in permeability is mediated by O2 radicals. The increased permeability occurs primarily in penetrating arterioles and not in pial arterioles or veins.

Superoxide Generation Links Nociceptin/Orphanin FQ (NOC/oFQ) Release to Impaired N -Methyl- d -Aspartate Cerebrovasodilation After Brain Injury

“…For example, it was hypothesized that acute elevations of blood pressure after injury in the adult result in the release and metabolism of arachidonic acid, which would generate oxygen free radicals, causing cerebral functional abnormalities. 27,31,32,35 However, in contrast to studies performed in adult and juvenile animals, there was no acute elevation in blood pressure after FPI in the newborn pig. 8 Because the elevation in systemic blood pressure was thought to be an absolute requirement for cerebral generation of free radicals after injury, 27,31,32,35 the observed decrease in blood pressure was perplexing initially.…”

“…31 In that study, the sustained dilation and abnormal responsiveness of pial arterioles observed after injury could be reversed by treatment with the free radical scavengers SOD and catalase. 31 Oxygen radicals also have been shown to increase blood-brain barrier permeability, 32 produce ultrastructural changes in pial vessel endothelium, 32 and cause abnormal arteriolar reactivity. 33 In addition, oxygen radical scavengers have been shown to improve vascular function and blood flow during focal ischemia in rats, which may account for the observed reductions in infarct size.…”

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

“…the rate at which SOD converts the superoxide anion to HµOµ. These two antioxidants were also needed to block induced increases in albumin extravasation seen by Wei et al (1986). Desferrioxamine also prevented the permeability response to arachidonic acid at modest concentrations (100 ìÒ rather than > 1 mÒ), which relates to its ability to prevent lipid peroxidation rather than direct free radical formation (Caraceni, Vanthiel & Borle, 1995).…”

Angiotensin II AT 1 Blockade Normalizes Cerebrovascular Autoregulation and Reduces Cerebral Ischemia in Spontaneously Hypertensive Rats

“…In addition, blockade of AT 1 receptors could also decrease the stimulation of superoxide and peroxynitrite production by Ang II in blood vessels. 25,26 Superoxide ion formation by Ang II could produce cytotoxic effects, including increases in blood-brain barrier permeability, 27 and this may explain the decrease in cerebral edema after candesartan pretreatment. In addition, peripheral administration of candesartan inhibits AT 1 receptor binding in brain areas such as the nucleus of the solitary tract, contributing to regulate cerebrovascular flow through modulation of central sympathetic activity and in turn modulation of the brain Ang II system 12,28 and in the middle cerebral artery.…”