A Potent Protective Role of Lysophospholipids against Global Cerebral Ischemia and Glutamate Excitotoxicity in Neuronal Cultures

摘要: Lysophospholipids (LPLs) are important intermediates in the synthesis and degradation of membrane phospholipids. Here we show that certain LPLs, particularly lysophosphatidylcholine lysophosphatidylinositol, prevent neuronal death both an vivo model transient global ischemia vitro excitotoxicity using primary cultures cerebellar granule cells exposed to high extracellular concentrations glutamate (20-40 micromol/L). The intravenous injection or lysophosphatidylinositol at a concentration 200 nmol/kg induced survival CA1 pyramidal neurons as approximately 95%, even when treatment was started 30 minutes after 15-minute ischemia. In contrast, lysophosphatidic acid no protection. This work also provides evidence pretreatment with (200 nmol/kg) injected long 3 days before severe 6-minute provided potent tolerance against neurodegeneration. Neuroprotection observed experiments LPLs. Taken together, data suggest potential therapeutic use LPLs antiischemic compounds. role 2P-domain K+ channels targets this neuroprotective effect is discussed.