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Platelet‐activating factor antagonists reduce excitotoxic damage in cultured neurons from embryonic chick telencephalon and protect the rat hippocampus and neocortex from ischemic injury in vivo
Author(s) -
Prehn Jochen H. M.,
Krieglstein J.
Publication year - 1993
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.490340205
Subject(s) - neocortex , neuroprotection , biology , hippocampus , glutamate receptor , cerebrum , hippocampal formation , excitatory postsynaptic potential , ischemia , pharmacology , endocrinology , neuroscience , medicine , anesthesia , central nervous system , inhibitory postsynaptic potential , receptor , biochemistry
The neuroprotective effects of the platelet‐activating factor (PAF) antagonists BN 52020 and BN 52021 were determined in a temperature‐controlled model of transient forebrain ischemia in the rat (occlusion of both common carotid arteries combined with lowering of the mean arterial blood pressure to 40 mm Hg for 10 min). After 7 days of recirculation, the ischemic neuronal damage was evaluated histologically within the hippocampus and neocortex. Combined pre‐ and post‐treatment with the PAF antagonists (2 × 25 mg/kg, s.c.) significantly reduced the resulting neuronal damage of the CA1 and CA3 hippocampal subfields and of the occipital and parietal cerebral cortex. The two PAF antagonists were also tested for their neuroprotective activity in primary neuronal cultures isoalted from embryonic chick telencephalon. Since an excessive activation of excitatory amino acid receptors is discussed to be of importance for the ischemic brain damage, the cultured neurons were exposed to the excitatory amino acid L‐glutamate (1 mM) for a period of 60 min. Twenty hours after the excitotoxic insult, BN 52020‐ and BN 52021‐ treated cultured (1–100 μM) showed both a better preserved morphology, as well as a dose‐dependent increase in cell viability and protein content compared to the control cultures. Our results demonstrate that the PAF antagonists BN 52020 and BN‐52021 have the capacity to protect brain tissue against ischemic neuronal damge independent of hypothermic effects and are also capable of reducing excitotoxic damage of telencephalic neurons from chick embryos cultured in the absence of glial or endothelial cells. We thus propose that PAF plays an important role in the pathophysiology of ischemic/excitotoxic neuronal injury via a direct action on neurons. © 1993 Wiley‐Liss, Inc.