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

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

Cited literature [64 references]  Display  Hide  Download

https://hal.archives-ouvertes.fr/hal-02266278
Contributor : Nicolas Blondeau <>
Submitted on : Wednesday, August 14, 2019 - 12:03:34 PM
Last modification on : Thursday, August 15, 2019 - 1:13:56 AM

File

2002-JCbfm.PDF
Publisher files allowed on an open archive

Identifiers

Collections

Citation

Nicolas Blondeau, Inger Lauritzen, Catherine Widmann, Michel Lazdunski, Catherine Heurteaux. A Potent Protective Role of Lysophospholipids Against Global Cerebral Ischemia and Glutamate Excitotoxicity in Neuronal Cultures. Journal of Cerebral Blood Flow and Metabolism, Nature Publishing Group, 2016, 22 (7), pp.821-834. ⟨10.1097/00004647-200207000-00007⟩. ⟨hal-02266278⟩

Share

Metrics

Record views

12

Files downloads

5