Document Detail


Early evolution and recovery from excitotoxic injury in the neonatal rat brain: a study combining magnetic resonance imaging, electrical impedance, and histology.
MedLine Citation:
PMID:  7929643     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We explored the therapeutic potentials of two N-methyl-D-aspartate (NMDA) receptor antagonists in vivo using different techniques. NMDA injected into the striatum of neonatal rats (20 nmol/0.5 microliters) induced a rapid increase in the diffusion-weighted (DW) image intensity, spreading over a large part of the ipsilateral hemisphere. Subcutaneous injection of the NMDA receptor antagonist MK-801 (1 mg/kg) or D-(E)-4-(3-phosphono-2-prop-enyl)-2-piperazine-carboxylic acid (D-CPPene; 1.5 mg/kg) reversed both the volume and the grading of the NMDA-induced hyperintensity of DW images, the reversal by MK-801 being more rapid than that by D-CPPene. In the cerebral cortex, there was an inverse relationship between changes in DW image intensity and the size of the extracellular space, assessed by electrical impedance measurements. The reduction of the hyperintense volume in DW images 1 or 2 h after MK-801 or D-CPPene treatment of NMDA-injected animals depended on the type of antagonist used and on the interval between intrastriatal NMDA injection and antagonist treatment. The reduction was 95% when MK-801 was given with a delay of 90 min and decreased to 20% when it was given at 360 min. With D-CPPene, the reduction was 80% after a delay of 30 min and virtually absent when it was administered at 360 min. Quantitative analysis showed significant correlations between the residual hyperintense volume 1 or 2 h after MK-801 or D-CPPene treatment and the final lesion volume, assessed from either T2-weighted images (R = 0.89, p < 0.001) or histology (R = 0.80, p < 0.001) 5 days after the insult. This study illustrates the sensitivity of DW magnetic resonance imaging to monitor in vivo early events after an excitotoxic insult and the effect of putative protective drugs that may counteract the resulting damage.
Authors:
M van Lookeren Campagne; J B Verheul; K Nicolay; R Balázs
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  14     ISSN:  0271-678X     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  1994 Nov 
Date Detail:
Created Date:  1994-11-21     Completed Date:  1994-11-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1011-23     Citation Subset:  IM    
Affiliation:
F. Hoffmann-LaRoche Ltd., Central Nervous System Department, Basel, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn
Brain / drug effects*,  pathology
Brain Injuries / diagnosis*,  pathology,  physiopathology*
Dizocilpine Maleate / pharmacology
Electric Conductivity
Magnetic Resonance Imaging
N-Methylaspartate / antagonists & inhibitors,  pharmacology*
Neurotoxins / pharmacology*
Piperazines / pharmacology
Rats
Wound Healing*
Chemical
Reg. No./Substance:
0/Neurotoxins; 0/Piperazines; 137424-80-7/SDZ EAA 494; 6384-92-5/N-Methylaspartate; 77086-22-7/Dizocilpine Maleate
Comments/Corrections
Erratum In:
J Cereb Blood Flow Metab 1995 Jul;15(4):719

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


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