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.

Altered splenic catecholamine concentrations during experimental allergic encephalomyelitis.

Catecholamine concentrations of the spleen were studied with neurochemical techniques in rats injected with myelin basic protein to produce an experimental allergic encephalomyelitis (EAE). Thirteen to 14 days postinoculation the affected rats showed peak clinical signs of weakness, especially in the lower extremities. Resolution of the disease then progressed rapidly with full clinical recovery at day 21. Splenic concentrations of norepinephrine (NE), 3,4-dihydroxyphenylalanine (DOPA), epinephrine (EPI) and 3,4-dihyxroxyphenylethylamine (DA) were determined by HPLC with electrochemical detection. DOPA concentrations were significantly increased (+62%) while DA concentrations were decreased (-29%) in the EAE rats on day 14 postinoculation. NE and EPI concentrations tended to be elevated in the EAE group, but this was not statistically significant. No differences in splenic catecholamines were detected on day 7 and 52 postinoculation between EAE and control animals. These results indicate that changes in the metabolic pathways of splenic catecholamines occur at the peak of the clinical symptoms of EAE; the increase in DOPA and the decrease in DA concentrations suggest that the activity of DOPA-decarboxylase or its co-factor is altered.