Expression of group II phospholipase A2 in rat brain after severe forebrain ischemia and in endotoxic shock.

Secretory phospholipase A2 type II is known to be involved in various inflammatory processes. This paper describes the changes in secretory phospholipase A2 (PLA2) gene expression induced by ischemia and endotoxic shock. Type I PLA2 (pancreatic type) is not expressed in ischemic and endotoxic-shock brains but both ischemia and endotoxin injection induce type II PLA2 expression. The first phase of PLA2 II gene expression following the ischemic insult occurs 1-6 h after ischemia. During that period, PLA2 II gene expression is slightly enhanced and it returns to control levels after 1 day. A second phase corresponding to higher levels of induction of mRNA for PLA2 appears at a later period after ischemia between 7 and 18 days. In situ hybridization shows that PLA2 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 PLA2 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 PLA2 gene expression could be an additional element in mechanisms leading to neuronal death. The later phase of increased PLA2 mRNA levels is more probably related to the inflammatory response associated to neuronal degeneration.