Stroke, Vol 23, 1125-1130, Copyright © 1992 by American Heart Association
Y Ueda, TP Obrenovitch, SY Lok, GS Sarna and L Symon
BACKGROUND AND PURPOSE: Evidence suggesting that ischemia-induced neuronal
damage may be linked to an extracellular overflow of glutamate has
accumulated, and previous studies have shown that repetitive ischemic
insults may have a cumulative effect. The purpose of this study was to
investigate changes in the extracellular glutamate concentration produced
by repeated brief ischemic episodes of varied severity. METHODS: Four
consecutive 3- or 5-minute periods of bilateral hemispheric ischemia were
produced in rats, each ischemic period followed by 27 minutes of
reperfusion. Extracellular glutamate in the striatum was monitored using
microdialysis, and the electroencephalogram and extracellular direct
current potential were recorded in the same tissue site to assess the
severity of ischemia. RESULTS: The results suggest that the kinetics of the
increase in the extracellular glutamate concentration produced by a brief
ischemic episode are similar, irrespective of whether it is a single insult
or part of a repeated sequence. In all cases, the extracellular glutamate
concentration increased throughout ischemia and returned to its preischemic
level early during reperfusion. The pattern of changes in the
ischemia-induced glutamate overflow during repetitive insults varied with
the severity of ischemia, in common with the pattern of changes in the
direct current potential, supporting the concept that ionic changes
associated with anoxic depolarization are a major determinant of
ischemia-induced glutamate overflow. CONCLUSIONS: There may be no
cumulative effect of brief repeated episodes of ischemia on the
extracellular glutamate concentration, even though repeated 5- minute
ischemic episodes apparently caused progressive deterioration of ionic
homeostasis in some cases.
ARTICLES
Changes in extracellular glutamate concentration produced in the rat striatum by repeated ischemia [published errata appear in Stroke 1993 Apr;24(4):616 and 1993 Jun;24(6):912-3]
Gough-Cooper Department of Neurological Surgery, Institute of Neurology, London, England.
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