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Structural damage of the ischemic brain: Involvement of calcium and effects of postischemic treatment with calcium entry blockers
Author(s) -
van Reempts Jos,
Haseldonckx Marc,
van Deuren Bruno,
Wouters Luc,
Borgers Marcel
Publication year - 1986
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430080145
Subject(s) - nimodipine , flunarizine , ischemia , hippocampal formation , calcium , cell damage , brain damage , anesthesia , medicine , neuronal damage , verapamil , pharmacology , chemistry , cardiology , endocrinology , biochemistry
The consequences of acute cerebral ischemia and the protective effects of post‐treatment with flunarizine and nimodipine were morphologically studied in an experimental rat model allowing simple quantification of delayed neuronal damage. Global incomplete ischemia was induced by temporary clamping of both carotid arteries combined with severe hypotension. Selective damage to CA1 hippocampal neurons was quantified 7 days later. Cytochemical visualization of subcellular Ca 2+ in this model revealed a correlation between irreversible cell necrosis and toxic cytosolic Ca 2+ ‐overload, the latter being a relatively slow process originating late in the reoxygenation period. Treatment with Ca 2+ ‐entry blockers started at 5 min after restoration of cerebral blood flow. Flunarizine significantly protected against ischemic hippocampal damage, whereas nimodipine had no effect.