|Budget Amount *help
¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1995 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1994 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1993 : ¥700,000 (Direct Cost : ¥700,000)
After intracranial hemorrhage, iron ions are liberated by the breakdown of red blood cells, and then active oxygens are generated in brain tissue by iron-mediated reactions. These radicals form an convulsive guanidino compounds, and also may be responsible for the initiation of lipid peroxidation in neural membranes. Injury to the membranes impairs neuronal activity and causes disrupts neuro-transmission. These disorders may lead to early seizures, which is a major risk factor for the development of post-traumatic epilepsy. Therefore, when active oxygens are removed from the focal area, the subsequent steps may not occur and the formation of epileptic foci may be avoided.
In the present studies, I focused on the effects of some radical scavengers, such as (-) -epigallocatechin (EGC), EGC-3-O-gallate (EGCG), _L-ascorbic acid 2- [3,4-di-hydro-2,5,7,8-tetramethyl-2- (4,8,12-trimethyltridecyl) -2H-1-benzopyran-6-yl hydrogen phosphate] potassium salt (EPC), adenosine (Ado) and 2-chloroadenos
ine (Cl-Ado), on physiological and neurochemical changes in an experimental model of post-traumatic epilepsy induced by ferric chloride injction. To suppress the occurrence of epileptic discharges induced by FeCl_3 injection, (1)EGC and EGCG inhibit dopaminergic hyperactivity via activation of serotonergic neurones and production of convulsive guanidino compounds, (2)EPC activated suppressive dopaminergic neurons, and (3)Ado and Cl-Ado scavenged active oxygens. It might is accompanied with formation of an epileptic focus that nitric oxide synthase (NOS), of which product may act as an endogenous anticonvulsant, decreased.
I conclude that the occurrence of post-traumatic epilepsy may be prevented by using active oxygen scavengers as preventive preparations. Active oxygens have been also suggested to be involved in a number of human disease processes such as cancer, ischemia, epilepsy, aging, and other diseases. Therefore, these active oxygen scavengers may also be useful as a clinical agent in the prevention, treatment and the attenuation of such free radical-induced degenerative diseases. Less