Effects of cyclic phosphatidic acid on delayed neuronal death following transient ischemia in rat hippocampal CA1.
Cyclic phosphatidic acid (cPA) is a lipid mediator that elicits a neurotrophin-like action in embryonic hippocampal neurons in vitro. In this study, we investigated the effects of cPA and 2-O-carba-oleoyl-cPA (2ccPA), a metabolically stabilized cPA derivative, on ischemia-induced delayed neuronal death in the rat hippocampal CA1 region. Transient occlusion for 8 min of bilateral carotid arteries besides permanent ligation of bilateral vertebral arteries was performed and morphological changes of the neurons were examined histologically 5 days after occlusion. cPA or 2ccPA was continuously administered for 5 days by means of an osmotic pump that was implanted subcutaneously before occlusion. Five days after occlusion, delayed neuronal death occurred in approximately 85% of the CA1 hippocampal neurons in the 0.2-2% bovine serum albumin vehicle control group. However, administration of cPA significantly increased the number of undamaged neurons in a dose-dependent manner. At the most effective concentration (18 μg/kg/5d), the number of undamaged neurons was increased to 4 times of that in the vehicle control group. 2ccPA also showed a neuroprotective effect, but it was less potent than that of natural cPA. These results indicate that systemic administration of both cPA and 2ccPA can protect neurons from ischemia-induced delayed neuronal death in the hippocampus.
Gotoh
Mari
M
Department of Biology, Faculty of Science, Ochanomizu University, 2-1-1 Ohtsuka, Bunkyo-ku, Tokyo 112-8610, Japan.
Hotta
Harumi
H
Murakami-Murofushi
Kimiko
K
D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D055104:Infusions, Subcutaneous; D002546:Ischemic Attack, Transient / Q000188:drug therapy*; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010712:Phosphatidic Acids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
C000610718:1-oleoyl-2-carba cyclic phosphatidic acid; C515244:3-O-carba-oleoyl-cyclic phosphatidic acid; D018696:Neuroprotective Agents; D010712:Phosphatidic Acids; D020033:Protein Isoforms; D012333:RNA, Messenger; D049368:Receptors, Lysophosphatidic Acid