title: Effects of delayed treatment with nafronyl oxalate on microsphere embolism-induced changes in monoamine levels of rat brain regions.
abstract: 1. The present study was undertaken to examine the effects of delayed treatment with nafronyl oxalate (nafronyl), a cerebral vasodilator, on monoamine neurotransmitters of brain regions in the microsphere-embolized rat. 2. Microsphere embolism was induced by injecting 900 microspheres with a diameter of 48 microns into the right internal carotid artery of rats. Microsphere-embolized rats were treated with nafronyl, 15 mg kg-1, i.p., twice daily from the first to the 5th day. Levels of monoamines and their metabolites in the cerebral cortex, striatum, and hippocampus were measured on days 3 and 5 after the operation by a high-performance liquid chromatograph with electrochemical detection. In vivo tyrosine or tryptophan hydroxylation was estimated by measurement of the accumulation of 3, 4-dihydroxyphenylalanine or 5-hydroxy-1-tryptophan after administration of 3-hydroxybenzylhydrazine dihydrochloride, an inhibitor of aromatic L-amino acid decarboxylase. 3. Microsphere embolism induced decreases in dopamine, noradrenaline and 5-hydroxytryptamine in three brain regions of the right hemisphere on days 3 and 5. In the left hemisphere, the monoamines were reduced, but to a lesser degree than in the right hemisphere. On days 3 and 5, the decrease in the monoamines of the right hemisphere was attenuated by nafronyl treatment except for noradrenaline on day 3. The decrease in the monoamines levels in the left hemisphere was almost completely prevented by nafronyl treatment. 4. On day 3 after microsphere embolism, in vivo tyrosine and tryptophan hydroxylation was lower than the pre-embolic value in all three brain regions. Treatment of the embolized rats with nafronyl significantly attenuated the decrease in in vivo tyrosine and tryptophan hydroxylation in the ipsilateral hemisphere, but not hippocampal tryptophan hydroxylation. 5. The results suggested that treatment with nafronyl improves or attenuates changes in monoamine neurotransmitter metabolism of the brain regions impaired by microsphere embolism. The mechanisms underlying this effect may be attributed to preservation of the ability to synthesize monoamines when the brain is ischaemic or oligaemic.
authors: Department of Pharmacology, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.
authors: N
authors: N
authors: Takagi
authors: K
authors: K
authors: Miyake
authors: A
authors: A
authors: Ohiwa
authors: R
authors: R
authors: Nukaga
authors: S
authors: S
authors: Takeo
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D006900:Hydroxylation; D002542:Intracranial Embolism and Thrombosis / Q000378:metabolism*; D008297:Male; D008863:Microspheres; D009257:Nafronyl / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D013997:Time Factors; D014364:Tryptophan / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D015306:Biogenic Monoamines; D018377:Neurotransmitter Agents; D014665:Vasodilator Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D009257:Nafronyl; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan; D004298:Dopamine; D009638:Norepinephrine