Prevention of hippocampus neuronal damage in ischemic gerbils by a novel lipid peroxidation inhibitor (quinazoline derivative).

Abstract

We investigated the effect of a novel quinazoline derivative (KB-5666), a lipid peroxidation inhibitor, on ischemic neuronal damage using Mongolian gerbils. The animals were sacrificed 7 or 30 days after 5 min of forebrain ischemia induced by bilateral common carotid artery occlusion. Morphologic changes, a microtubule-associated protein 2 (MAP2) immunohistochemical study and quantitative autoradiographic study using [3H]phorbol 12, 13-dibutyrate ([3H]PDBu) were evaluated in the hippocampus after ischemia. KB-5666 (3-50 mg/kg, i.v.) showed protective effects against neuronal death of the CA1 subfield 5 min before ischemia, immediately or 1 hr after ischemia, but not 4 hr after ischemia. KB-5666 (i.p.) also showed protective effects in a dose-dependent manner immediately after ischemia. Furthermore, KB-5666 dose-dependently prevented a marked decrease in microtubule-associated protein 2 immunoreactivity in the dendritic fields of the CA1 pyramidal cells after ischemia. The [3H]PDBu binding activity in the stratum oriens and the stratum lacunosum-moleculare of the CA1 subfield was reduced by 19 and 30%, respectively, 7 days after ischemia. [3H]PDBu binding sites were unchanged in the stratum oriens in the CA3 subfield. By contrast, in the molecular layer of the dentate gyrus, the [3H]PDBu binding activity increased by 15%. KB-5666 (i.v.) prevented a decrease in the [3H]PDBu binding activity in the stratum oriens and stratum lacunosum-moleculare of the CA1 subfield and an increase in the molecular layer of the dentate gyrus. These histologic, immunohistochemical and receptor-autoradiographic data indicate that KB-5666 protects the brain from both cellular and functional consequences of ischemia.

• Authors: H Hara, K Kogure
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 255 Issue 2 Pg. 906-13 (Nov 1990) ISSN: 0022-3565 [Print] United States
• PMID: 2243357 (Publication Type: Journal Article)

Chemical References

• Free Radicals
• Microtubule-Associated Proteins
• Quinazolines
• KB 5666
• Phorbol 12,13-Dibutyrate
• Pentobarbital

Topics

• Animals
• Autoradiography
• Brain Ischemia (pathology)
• Free Radicals
• Gerbillinae
• Hippocampus (drug effects, pathology)
• Lipid Peroxidation (drug effects)
• Male
• Microtubule-Associated Proteins (analysis)
• Neurons (drug effects, pathology)
• Pentobarbital (pharmacology)
• Phorbol 12,13-Dibutyrate (metabolism)
• Quinazolines (pharmacology)