Suppression of clinical weakness in experimental autoimmune encephalomyelitis associated with weight changes, and post-decapitation convulsions after intracisternal-ventricular administration of 6-hydroxydopamine.
Selective depletion of central nervous system norepinephrine (NE) by the neurotoxin 6-hydroxydopamine (6-OHDA) in rats subsequently inoculated with myelin basic protein (MBP) and complete Freund's adjuvant (CFA) produced experimental autoimmune encephalomyelitis (EAE) without the usual expected degree of weakness. The preservation of strength occurred in spite of continued weight loss. Post-decapitation myoclonic convulsive kick latency and kick number, which are known to depend on spinal cord NE, agreed well with the degree of weakness through the clinical disease course. The only difference between EAE groups was that the stronger 6-OHDA pretreated EAE animals did not have an elevated pons-medulla NE compared to saline intracisternal-ventricular (i.c.v.) pretreated controls. We conclude that 6-OHDA can influence the clinical course of weakness by interfering with central noradrenergic activity independent of other features associated with disease in EAE. This effect of 6-OHDA may be exerted through alteration of the blood-spinal cord barrier function and/or central nervous system blood flow.
Department of Neurology, Medical College of Wisconsin, Milwaukee.
R J
RJ
Konkol
U
U
Wesselmann
W J
WJ
Karpus
G L
GL
Leo
J A
JA
Killen
D L
DL
Roerig
D000818:Animals; D001835:Body Weight; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D002395:Catecholamines / Q000378:metabolism; D002552:Cerebral Ventricles; D002946:Cisterna Magna; D003655:Decerebrate State; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D005620:Freund's Adjuvant / Q000494:pharmacology; D006892:Hydroxydopamines / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D004676:Myelin Basic Protein / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine; D051381:Rats; D011917:Rats, Inbred Lew; D012640:Seizures / Q000209:etiology / Q000503:physiopathology*
D002395:Catecholamines; D006892:Hydroxydopamines; D004676:Myelin Basic Protein; D016627:Oxidopamine; D005620:Freund's Adjuvant; D009638:Norepinephrine