| Co-Investigator(Kenkyū-buntansha) |
MIZUKAWA Kiminao Okayama Univ. Med. Sch., Instructor, 医学部, 講師 (40137154)
NISHIMOTO Akira Okayama Univ. Med. Sch., Professor, 医学部, 教授 (50032850)
WATANABE Yoko Okayama Univ. Med. Sch., Assistant, 医学部, 助手 (70135945)
HIRAMATSU Midori Okayama Univ. Med. Sch., Assistant, 医学部, 助手 (70124790)
YOKOI Isao Okayama Univ. Med. Sch., Assistant, 医学部, 助手 (80150366)
|
|---|
| Research Abstract |
We studied on pathogenesis of post-traumatic epilepsy using iron- induced epileptic rats as an experimental post-traumatic epilepsy, and also on rational treatments for it, being based on these experimental results. 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. We observed that iron liberated from hemoglobin is associated with generation of active oxygen species, such as O^-_ and .OH. Moreover, we demonstrated that hemoglobin itself promotes oxygen free radical generation.
Then we estimated accelerated production of thiobarbituric acid reactive substances (TBARS), and suggested that oxygen free radicals, especially .OH is responsible for the induction of peroxidation of neuronal lipids, that is an injury of neuronal membranes. On the other hand, we demonstrated that .OH accelerates 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. Then, we found that treatment of epigallocatechin(EGC) or a phosphate diester of vitamins E and C (EPC), which are a potent .OH scavenger and anti-oxidant, significantly inhibited the formation of malondialdehyde and epileptic discharges in the iron induced epileptic focus.
|
