Springer Online Journal Archives 1860-2000
Summary Cerebral microvessels receive a noradrenergic innervation originating from the locus coeruleus. Previously, many studies have tried to elucidate the role of the central noradrenergic innervation on the blood-brain barrier (BBB). Many of them are based on chemical destruction of the innervation by local injection of 6-hydroxydopamine (6-OHDA) or physical injury to the locus coeruleus. Such methods are not selective and the results reported are contradictory. We have treated mice with a single i. p. injection of the compound,N-2-chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP4). This substance induces a selective noradrenaline depletion and, unlike 6-OHDA, it can pass into the brain afer an i. p. injection. The animals were allowed to survive for 6 h to 60 days and the BBB was investigated with i.v.-injected horseradish peroxidase (HRP). Brain density values were also determined to find out if edema developed. The light microscopic distribution of HRP in the brain of DSP4-treated animals did not differ from that in control mice, i.e., there were no signs of increased BBB permeability to this protein tracer caused by DSP4. Density determinations revealed statistically significant reduced values in cerebrum (P〈0.005) and rhombencephalon (cerebellum) (P〈0.0005) of animals given 100 mg/kg body wt. of DSP4 indicating development of edema. A minor drop in density of the rhombencephalon (cerebellum) (P〈0.05 at 48 h) and of the cerebrum (statistically not significant) appeared when 50 mg/kg body wt. of DSP4 was injected. Our findings indicate that the BBB to proteins maintains its function but that edema, likely composed of an ultrafiltrate from the blood, will develop after an injection of DSP4. In view of its selective degenerative action on the noradrenergic central neurons, this kind of brain edema is probably a direct consequence of abnormal noradrenergic innervation of the cerebral blood vessels. Our observations are thus in line with the assumption that the noradrenergic innervation influences endothelial permeability in the central nervous system. Alternative pathogenetic mechanisms are discussed.
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