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Comparative protective effects of nicardipine, flunarizine, lidoflazine and nimodipine against ischaemic injury in the hippocampus of the Mongolian gerbil
Author(s) -
Alps B.J.,
Calder C.,
Hass W.K.,
Wilson A.D.
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb11475.x
Subject(s) - nimodipine , nicardipine , flunarizine , gerbil , medicine , anesthesia , common carotid artery , hippocampus , hippocampal formation , cinnarizine , saline , ischemia , pharmacology , carotid arteries , calcium
1 Morphological changes characterizing delayed neuronal death (DND) of selectively vulnerable CA 1 pyramidal cells in the hippocampus of the Mongolian gerbil brain occurred 72 h after transient (5 min) bilateral occlusion of the common carotid arteries. 2 Different groups of animals were treated 15 min before carotid artery occlusion and twice daily during the 72 h post‐ischaemia period with either saline alone, nicardipine, flunarizine, lidoflazine or nimodipine at doses of 500 μg kg −1 intraperitoneally. 3 At 72 h the animals were killed and their brains examined histologically. Absolute cell counts were made from 5 sites distributed linearly throughout the hippocampal CA 1 subfield in each hemisphere to determine the percentage DND in each group. Normal brains and those of sham‐operated animals were included in the study for comparison. 4 Features of DND were distributed evenly throughout the CA 1 subfield in both hemispheres in all groups of gerbils. Nicardipine, lidoflazine and flunarizine, but not nimodipine, were protective. This protection extended linearly throughout the hippocampus without altering the pattern of neuronal damage. 5 Compared to saline‐treated (78.3 ± 2.9% DND) and nimodipine‐treated (76.5 ± 3.4% DND) gerbils, the overall protection afforded by nicardipine (41.8 ± 3.8% DND) was statistically significant. The effects of lidoflazine (53.6 ± 7.1%) and flunarizine (55.8 ± 3.9% DND) were of borderline significance. 6 Abnormal neurones appeared in normal and sham‐operated brains to the extent of 4.5 ± 1.0% and 4.6 ± 0.4%, respectively. Such changes can be attributed to fixation artefacts. 7 The results demonstrate that overall protection is conferred on ischaemic hippocampal CA 1 neurones by nicardipine and to a lesser extent by flunarizine and lidoflazine, but not by nimodipine.