Neurochemical changes and laser Doppler flowmetry in the endothelin-1 rat model for focal cerebral ischemia.
Generalized neurotransmitter overflow into the extracellular space, after cerebral ischemia, has been suggested to contribute to subsequent neuronal death. This study aims to investigate the striatal release of the neurotransmitters dopamine (DA), glutamate (Glu) and gamma-aminobutyric acid (GABA) by means of microdialysis, in a rat model for focal transient cerebral ischemia. Ischemia was induced by the application of 120 pmol endothelin-1 (Et-1), adjacent to the middle cerebral artery (MCA) in freely moving rats. Ischemia produced a large increase in extracellular striatal DA concentrations (2400%), Glu (5500%) and GABA (800%) concentrations. Laser Doppler flowmetry in anaesthetized rats, indicated that the blood flow within the striatum decreased by 75+/-11%. The period of sustained drop of blood flow, was dose-dependently related to the concentration Et-1 injected. Histological analysis of brain slices, taken from anaesthetized and conscious animals, indicated a 500 pmol dose of Et-1 was required to produce a similar infarct in anaesthetized rats to a 120 pmol dose of Et-1 in freely moving rats. The immediate drop in striatal blood flow, and the prompt increase of extracellular DA, after the micro-application of Et-1, were quite striking. This suggests that the DA release, rather than the Glu overflow may be the primary event initiating the cascade of processes ultimately leading to cell death and neurological deficits.
Bogaert
L
L
Department of Pharmaceutical Chemistry and Drug Analysis, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
Scheller
D
D
Moonen
J
J
Sarre
S
S
Smolders
I
I
Ebinger
G
G
Michotte
Y
Y
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000633:toxicity; D018698:Glutamic Acid / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D017078:Laser-Doppler Flowmetry; D008297:Male; D017551:Microdialysis; D020768:Middle Cerebral Artery; D051381:Rats; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D019332:Endothelin-1; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D004298:Dopamine