Lipid peroxides in the free radical pathophysiology of brain diseases

1. Polyunsaturated fatty acids are essential for normal neural cell membran e functioning because many membrane properties, such as fluidity and permea bility, are closely related to the presence of unsaturated and polyunsatura ted side chains. Lipid peroxidation results in loss of membrane polyunsatur ated fatty acids and oxidized phospholipids as polar species contributing t o increased membrane rigidity. 2. Polyunsaturated fatty acids are released from membrane phospholipids by a number of enzymic mechanisms involving the receptor-mediated stimulation of phospholipase A(2) and phospholipase C/diacylglycerol lipase pathways. 3. The overstimulation of excitatory amino acid (EAA) receptors stimulates the activities of lipases and phospholipases, and this stimulation produces changes in membrane phospholipid composition, permeability, and fluidity, thus decreasing the integrity of plasma membranes. 4. Alterations in properties of plasma membranes may be responsible for the degeneration of neurons seen in neurodegenerative diseases. Two major proc esses may be involved in neuronal injury caused by the overstimulation of E AA receptors. One is a large Ca2+ influx and the other is an accumulation o f free radicals and lipid peroxides as a result of neural membrane phosphol ipid degradation. It is suggested that calcium and free radicals act in con cert to induce neuronal injury in acute trauma (ischemia and spinal cord in jury) and in neurodegenerative diseases.