Document Detail

Extracellular perfusion of rat brain nuclei using microdialysis: a method for studying differential neurotransmitter release in response to neurotoxins.
MedLine Citation:
PMID:  10446406     Owner:  NLM     Status:  MEDLINE    
Microdialysis probes, stereotactically placed in rat brain nuclei, allow detailed kinetic comparisons of neurotransmitter release from in situ chemical lesioning over a continuum from acute early changes (minutes) to chronic late changes (days). This technique insures a localized mechanism of action independent of systemic effects apparent with other routes of administration and independent of mechanical damage patterns encountered in conventional chemical lesioning. The example provided compares changes in extracellular gamma-aminobutyric acid (GABA) concentrations in the striatum in response to quinolinic acid (QA, 0.24 M) and 3-nitropropionic acid (3-NPA, 0.25 M). These examples of chemical lesioning represent two theoretical mechanisms of neurodeterioration in Huntington's disease, QA representing the excitotoxic component, and 3-NPA representing the impaired mitochondrial energy component [M.F. Beal, N.W. Kowall, D.W. Ellison, M.F. Mazurek, K.J. Swartz, J.M. Martin, Replication of the neurochemical characteristics of Huntington's disease by quinolinic acid, Nature 321 (1986) 168-171; M.F. Beal, E. Brouillet, B.G. Jenkins, R.J. Ferrante, N.W. Kowall, J.M. Miller, E. Storey, R. Srivastava, B.R. Rosen, B.T. Hyman, Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid. J. Neurosci. 13 (1993) 4181-4192; N.C. Reynolds, W. Lin, C.M. Cameron, D.L. Roerig, Differential responses of extracellular GABA to intrastriatal perfusions of 3-nitropropionic acid and quinolinic acid in the rat, Brain Res. 778 (1997) 140-149]. An auxillary microdialysis probe implanted in the ipsilateral nucleus accumbens is used to define the physiologic extent of the cytotoxic lesion. Pre-column derivatization of perfusate fractions with o-phthalaldehyde/t-butylthiol (OPA) provides electroactivity to the OPA-GABA conjugate and facilitates electrochemical detection following high performance liquid chromatography [J.M. Peinado, K.T. McManus, R.B. Myers, Rapid method for microanalysis of endogenous amino acid neurotransmitters in brain perfusates in the rat by isocratic HPLC-EC, J. Neurosci. Methods 18 (1986) 269-276].
N C Reynolds; W Lin; C M Cameron; D L Roerig
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Brain research. Brain research protocols     Volume:  4     ISSN:  1385-299X     ISO Abbreviation:  Brain Res. Brain Res. Protoc.     Publication Date:  1999 Jul 
Date Detail:
Created Date:  1999-10-12     Completed Date:  1999-10-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9716650     Medline TA:  Brain Res Brain Res Protoc     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  124-31     Citation Subset:  IM    
Copyright Information:
Copyright 1999 Elsevier Science B.V.
Department of Neurology, The Medical College of Wisconsin, Milwaukee, WI, USA.
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MeSH Terms
Brain / drug effects*,  secretion
Chromatography, High Pressure Liquid
Corpus Striatum / drug effects,  secretion
Microdialysis / methods*
Neurons / drug effects,  secretion
Neurotoxins / pharmacology*,  toxicity
Neurotransmitter Agents / secretion*
Nitro Compounds
Nucleus Accumbens / drug effects,  secretion
Propionic Acids / pharmacology,  toxicity
Quinolinic Acid / pharmacology,  toxicity
Rats, Sprague-Dawley
Stereotaxic Techniques
Sulfhydryl Compounds
gamma-Aminobutyric Acid / secretion
Reg. No./Substance:
0/Neurotoxins; 0/Neurotransmitter Agents; 0/Nitro Compounds; 0/Propionic Acids; 0/Sulfhydryl Compounds; 504-88-1/3-nitropropionic acid; 56-12-2/gamma-Aminobutyric Acid; 643-79-8/o-Phthalaldehyde; 75-66-1/tert-butylthiol; 89-00-9/Quinolinic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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