EXPRESSION OF GROUP-II PHOSPHOLIPASE A(2) IN RAT-BRAIN AFTER SEVERE FOREBRAIN ISCHEMIA AND IN ENDOTOXIC-SHOCK

Secretary phospholipase A(2), type II is known to be involved in various inflammatory processes. This paper describes the changes in secretary phospholipase A(2) (PLA(2)) gene expression induced by ischemia and endotoxic shock. Type I PLA(2) (pancreatic type) is not expressed in ischemic and endotoxic-shock brains but both ischemia and endotoxin injection induce type II PLA(2) expression. The first phase of PLA(2) II gene expression following the ischemic insult occurs 1-6 h after ischemia. During that period, PLA(2) II gene expression is slighly enhanced and it returns to control levels after 1 day. A second phase corresponding to higher levels of induction of mRNA for PLA(2) appears at a later period after ischemia between 7 and 18 days. In situ hybridization shows that PLA(2) gene expression in the ischemic brain is localized in regions known to be vulnerable to ischemia (hippocampus and neocortex). Endotoxic shock which leads to a major inflammatory state induces an abundant expression of the PLA(2) II mRNA in the brain and this high level of expression appears in a large number of brain structures. The results suggest that the early phase of ischemia-induced PLA(2) gene expression could be an additional element in mechanisms leading to neuronal death. The later phase of increased PLA(2) mRNA levels is more probably related to the inflammatory response associated to neuronal degeneration.