Document Detail

Involvement of local ischemia in endothelin-1 induced lesions of the neostriatum of the anaesthetized rat.
MedLine Citation:
PMID:  1541348     Owner:  NLM     Status:  MEDLINE    
The present study examines the possibility that lesions induced by intrastriatal injections of endothelin-1 (ET-1, 0.43 nmol/0.5 microliter) are ischemic in nature due to a vasoconstriction of the cerebral microvessels. In time course and dose-response experiments with ET-1 and in comparisons with ET-3, the volume of the lesions has been determined based mainly on the disappearance of striatal nerve cells, using a computer assisted morphometrical analysis. The blood flow in the neostriatum close to the site of injection of ET-1 was determined acutely by Laser-Doppler flowmetry. The acute metabolic effects of ET-1 were also studied on striatal superfusate levels of lactate, pyruvate, dopamine and its metabolites DOPAC (3,4-dihydroxyphenylacetic acid) and homovanillic acid (HVA) using an intrastriatal microdialysis probe. Dose related striatal lesions were observed with ET-1 (0.043-0.43 nmol) with a peak lesion volume after 24-48 h and the possible existence of a penumbra area. ET-3 showed a reduced potency to produce striatal lesions compared to ET-1. The lesions induced by ET-1 were prevented by coinjection with dihydralazine, a vasodilator drug. Acutely ET-1 (0.43 nmol/0.5 microliter) produced a prolonged reduction of the cerebral blood flow down to 40% of control values and temporary increases of striatal lactate and DA efflux, the latter change being very marked. Also a significant reduction of DOPAC and HVA was observed. These neurochemical changes were all prevented by treatment with dihydralazine.(ABSTRACT TRUNCATED AT 250 WORDS)
K Fuxe; N Kurosawa; A Cintra; A Hallström; M Goiny; L Rosén; L F Agnati; U Ungerstedt
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Experimental brain research     Volume:  88     ISSN:  0014-4819     ISO Abbreviation:  Exp Brain Res     Publication Date:  1992  
Date Detail:
Created Date:  1992-04-03     Completed Date:  1992-04-03     Revised Date:  2013-12-13    
Medline Journal Info:
Nlm Unique ID:  0043312     Medline TA:  Exp Brain Res     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  131-9     Citation Subset:  IM    
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MeSH Terms
3,4-Dihydroxyphenylacetic Acid / metabolism
Brain Ischemia / chemically induced,  pathology*,  physiopathology
Cerebrovascular Circulation / drug effects*
Corpus Striatum / blood supply,  pathology*,  physiopathology
Dihydralazine / pharmacology
Dopamine / metabolism
Endothelins / administration & dosage,  toxicity*
Homovanillic Acid / metabolism
Lactates / metabolism
Microcirculation / drug effects,  pathology*,  physiopathology
Pyruvates / metabolism
Rats, Inbred Strains
Regional Blood Flow / drug effects
Stereotaxic Techniques
Reg. No./Substance:
0/Endothelins; 0/Lactates; 0/Pyruvates; 102-32-9/3,4-Dihydroxyphenylacetic Acid; PCU411F5L6/Dihydralazine; VTD58H1Z2X/Dopamine; X77S6GMS36/Homovanillic Acid

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