脳代謝研究施設機能生化学部門最近の研究概説(I) -外傷性てんかんの成因に関する研究-

Abstract

Post-traumatic epilepsy is characterized by epileptic seizures due to brain damage secondary to head injury, and it has been known since the days of Hippocrates. However, the pathogenesis of post-traumatic epilepsy in still unclear. Willmore et al (1978) first observed that injection of iron salts into the rat cortex induced a chronic epileptic focus (an experimental model of post-traumatic epilepsy). Head injury or hemorrhagic cortical infarction results in extravasation of blood and breakdown of red blood cells and hemoglobin. Biological iron is normally protein bound in hemoglobin and transferrin. Iron liberated from hemoglobin is thought to be associated with generation of active oxygen species. Moreover, hemoglobin itself may promote oxygen free radical generation. Oxygen free radicals, especially·OH is responsible for the induction of peroxidation of neuronal lipids, which causes damage to the neuronal membranes. On the other hand, ·OH accelerated the production of guanidino compounds in the brain, such as methylguanidine and guanidinoacetic acid. They are endogenous convulsants in the brain. These reactions may follow by excitatory and inhibitory neurotransmitter disorders, and may lead to development of epileptic discharges in the epileptogenic focus. Treatment with antioxidants such as epigallocatechin or a phosphate diester of vitamin E and C (EPC-K1), which are potent ·OH scavengers, may be useful for preventing development of the iron-induced epileptic focus.