ACTIVATION OF PHOSPHATIDYLINOSITOL BISPHOSPHATE SIGNAL-TRANSDUCTION PATHWAY AFTER EXPERIMENTAL BRAIN INJURY - A LIPID STUDY

Regional levels of phosphatidylinositol 4,5-bisphosphate (PLP(2)), dia cylglycerol (DG) and free fatty acids (FFA), involved in the signal tr ansduction pathway of the excitatory neurotransmitter system, were mea sured after lateral fluid percussion (FP) brain injury in rats. At 5 m in postinjury, tissue PIP2 concentrations were significantly reduced i n the cortices and hippocampi of both ipsilateral and contralateral he mispheres. Only levels of stearic and arachidonic acids were substanti ally decreased in PIP2 in these regions of the brain. At the same time after injury, both DG and FFA were significantly increased in the cor tices and hippocampi of both hemispheres. As was true for PIP2, only l evels of stearic and arachidonic acids markedly changed in both DG and FFA in these regions of the brain. At 20 min postinjury, a significan t decrease in PIP2 concentration and significant increases in levels o f DG and FFA were observed only in the injured left cortex. In additio n to the increases in stearic and arachidonic acids in FFA, increased amounts of palmitic and oleic acids were also found in the injured lef t cortex at 20 min after injury. These results suggest that the PIP2 s ignal transduction pathway is activated in the cortex and hippocampus at the onset of lateral FP brain injury and that the enhanced phosphol ipase C-catalyzed phosphodiestric breakdown of PLP(2) is a major mecha nism of liberation of FFA in these sites immediately after such injury .