Document Detail

Sequelae of parenteral domoic acid administration in rats: comparison of effects on different anatomical markers in brain.
MedLine Citation:
PMID:  9097394     Owner:  NLM     Status:  MEDLINE    
Brain damage following administration of domoic acid, a structural analog of the excitatory amino acids glutamic acid and kainic acid, was compared using different anatomic markers in adult rats. Seven days after administration of domoic acid (2.25 mg/kg i.p.) or vehicle, brains were collected and sectioned and stained to visualize Nissl substance using thionin, argyrophilia using a cupric silver staining method, astroglia using immunohistochemistry to detect glial fibrillary acidic protein-like immunoreactivity (GFAP-ir), and activated microglia using lectin histochemistry to detect Griffonia simplicifolia I-B4 isolectin (GSI-B4) binding in adjacent sections. In approximately 60% of rats to which it was administered, domoic acid caused stereotyped behavior within 60 min, followed by convulsions within 2-3 h. Brains of domoic acid-administered rats that did not manifest stereotyped behavior or convulsions did not differ from brains from vehicle-administered controls. In animals that had manifested stereotyped behavior and convulsions, Nissl staining was mostly unremarkable in brain sections. In contrast, there was intense argyrophilia in anterior olfactory nucleus, CA1 hippocampus, lateral septum, parietal (layer IV), piriform, and entorhinal cortices, ventral posterolateral thalamus, and amygdala. This pattern was reminiscent of that seen in postmortem specimens from humans who consumed domoic acid-tainted mussels and in experimental animals after kainic acid administration. Adjacent sections displayed astrogliosis, evidenced by increased GFAP-ir, which was more diffuse than the argyrophilic reaction. Activated microglia were revealed using GSI-B4 histochemistry. These data suggest activation of discrete brain circuits in rats that convulse following domoic acid administration and subsequent pathological alterations. The data strongly suggest that neuropathology following domoic acid occurs only in animals manifesting domoic acid-induced sterotypy and convulsions. The data do not rule out more insidious damage in behaviorally normal rats that receive domoic acid.
N M Appel; S I Rapoport; J P O'Callaghan
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Synapse (New York, N.Y.)     Volume:  25     ISSN:  0887-4476     ISO Abbreviation:  Synapse     Publication Date:  1997 Apr 
Date Detail:
Created Date:  1997-07-24     Completed Date:  1997-07-24     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8806914     Medline TA:  Synapse     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  350-8     Citation Subset:  IM    
Division of Applied Pharmacology Research, Food and Drug Administration, Laurel, Maryland 20708, USA.
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MeSH Terms
Astrocytes / drug effects,  pathology
Biological Markers
Brain / drug effects,  pathology*
Coloring Agents
Glial Fibrillary Acidic Protein / analysis*
Injections, Intraperitoneal
Kainic Acid / administration & dosage,  analogs & derivatives*,  toxicity
Microglia / drug effects,  pathology
Neurons / drug effects,  pathology*
Neurotoxins / administration & dosage,  toxicity*
Organ Specificity
Rats, Inbred F344
Grant Support
DA 224-91-130/DA/NIDA NIH HHS
Reg. No./Substance:
0/Biological Markers; 0/Coloring Agents; 0/Glial Fibrillary Acidic Protein; 0/Neurotoxins; 14277-97-5/domoic acid; 487-79-6/Kainic Acid

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

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