Levels of
phosphatidylinositol 4,5-bisphosphate (PIP2),
phosphatidylinositol 4-phosphate (PIP),
phosphatidylinositol (PI),
phosphatidic acid,
diacylglycerol (DAG),
triacylglycerol (TAG), and
free fatty acids (FFAs), as well as their
fatty acid composition, were determined in rat forebrain during
ischemia and postischemic recirculation. Cerebral energy state and electroencephalograms (EEGs) were also studied. Fifteen minutes of
ischemia resulted in a decrease in PIP2 and PIP contents but not in PI content, concurrent with an enlargement of the FFA and DAG pools. The latter were enriched in
stearate and arachidonate. Prolongation of
ischemia did not produce further changes in content of any of the
inositol phospholipids, but the increase in levels of FFAs and DAG continued. At the end of 45 min of
ischemia, levels of both PIP2 and PIP decreased by 45-50%, and the total
phosphoinositide content (PIP2 + PIP + PI) decreased by 21%, whereas levels of FFAs and DAG increased to 14- and 3.6-fold of control levels, respectively. During
ischemia, the TAG-
palmitate level decreased, but the TAG-arachidonate level increased; the tissue energy state deteriorated severely; and the EEG was suppressed. A 30-min recirculation period after 15 or 45 min of
ischemia led to increases in PIP2, PIP, and total
phosphoinositide contents, whereas levels of FFAs and DAG promptly decreased toward control values. The TAG-arachidonate level peaked and the TAG-
palmitate level returned to a low control value during early recirculation. The ischemic changes in tissue
lipids were completely reversed within 3 h of recirculation after both periods of
ischemia. Adenylates were fully phosphorylated with as little as 30 min of reflow. The EEG activity partially recovered during reflow after 15 min of
ischemia, whereas it remained depressed after prolonged
ischemia. Thus, phosphodiesteric cleavage of PIP2 and PIP followed by deacylation of DAG is likely to contribute to the production of FFAs in early
ischemia. Deacylation of undetermined
lipids plays a role for the increment in levels of FFAs in the later period of
ischemia. The rapid postischemic increase in levels of PIP2 and PIP indicates active synthesis not only from existing PI, but probably also by means of accumulated FFAs and DAG. These results indicate that the impaired resynthesis of
inositol phospholipids cannot be a cause of the poor EEG activity after prolonged
ischemia. Degradation and resynthesis of
polyphosphoinositides and formation of TAG-arachidonate may be important for modulation of free
arachidonic acid levels in the brain during temporary
ischemia.