[Experimental studies on the changes of mitochondrial membrane phospholipids during cerebral ischemia and...

Changes of brain mitochondrial phospholipids during cerebral ischemia and recirculation were experimentally studied in a rat 4-vessel occlusion model, to explore the relation between changes of mitochondrial phospholipids and dysfunction of mitochondria. Respiratory functions, activities of respiratory enzymes (cytochrome c oxidase, F0F1-ATPase) were analyzed after 30 and 60 minutes of ischemia, and after 30 minutes of recirculation following each ischemic period. Activities of respiratory functions and respiratory enzymes decreased progressively during ischemia, which recovered completely after recirculation following 30 minutes of ischemia, while only partial recovery was observed after recirculation following 60 minutes of ischemia. In phospholipid analyses, contents of phospholipid classes tended to decrease time-dependently during ischemia, and compositions of polyunsaturated fatty acids (PUFA) such as arachidonic acid (20:4) and docosahexaenoic acid (22:6) were decreased preferentially. In recirculation, phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cardiolipin (CL) showed recovery of contents of phospholipids and compositions of PUFA after recirculation following 30 minutes of ischemia, while further decrease of contents of phospholipids and compositions of PUFA were observed after recirculation following 60 minutes of ischemia, especially in CL. On the other hand, progressive degradation of phospholipids occurred after recirculation following both 30 and 60 minutes of ischemia in phosphatidylserine and phosphatidylinositol. Changes of major phospholipid classes such as PC, PE, and CL correlated with the changes of mitochondrial respiratory functions and activities of respiratory enzymes. In conclusion, changes of mitochondrial membrane phospholipids appear to affect the integrity of cellular energy metabolism via mitochondrial dysfunction during cerebral ischemia and recirculation.