Effects of the noradrenaline neurotoxin N-2-chloroethyl-N-ethyl-2-bromo-benzylamine hydrochloride (DSP4) on the blood-brain barrier. An experimental study in the mouse using protein tracer and density determination techniques.
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-bromo-benzylamine hydrochloride (DSP4). This substance induces a selective noradrenaline depletion and, unlike 6-OHDA, it can pass into the brain after 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 of 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 less than 0.005) and rhombencephalon (cerebellum) (P less than 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 less than 0.05 at 48 h) and of the cerebrum (statistically not significant) appeared when 50 mg/kg body wt. of DSP4 was injected.(ABSTRACT TRUNCATED AT 250 WORDS)
Tengvar
C
C
Institute of Pathology, Uppsala University, Sweden.
Pettersson
C A
CA
Mohammed
A K
AK
Olsson
Y
Y
D000818:Animals; D001596:Benzylamines / Q000008:administration & dosage / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002540:Cerebral Cortex / Q000473:pathology; D003720:Densitometry; D006735:Horseradish Peroxidase / Q000493:pharmacokinetics; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D009498:Neurotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D010539:Permeability; D012016:Reference Values
D001596:Benzylamines; D009498:Neurotoxins; D006735:Horseradish Peroxidase; C012102:DSP 4