EGb761 Co-administrated with FK506 Offer no More Neuroprotective Efficacy than EGb761 Alone during Focal Cerebral Ischemia and Reperfusion Monitored by Microdialysis Coupled with Microbore Liquid Chromatography

Abstract

Accumulated dopamine (DA) is believed to be detrimental to the brain. EGb761 and FK506 have been reported to possess neuroprotective efficacy. This study attempted to investigate the metabolic pathway of dopamine and to realize whether the synergistic effect would be achieved when EGb761 co-administrated with FK506. Dynamic changes of dopamine and its metabolites including 3, 4-dihydroxyphenylacetate (DOPAC), homovanillic acid (HVA) and 3-methoxytyramine (3-MT) in the striatum were measured. Histological technique of 2, 3, 5-triphenyltetrazolium chloride (TTC) staining was used for assessing the infarction volume. Data indicated that an approximately 80, 90, and 180 fold increases of the dopamine level was seen in the group of EGb761, control, and combination (EGb761 plus FK506) during ischemia. Interestingly, no significant changes in the level of DOPAC, HVA, and 3MT were observed among these groups. Histological evidence showed that the mean total infarction size was significantly elevated in the combination group when compared with the control group (P<0.05). Importantly, compared with the control group, the infarction volume at the slices of 4mm on the striatum was significantly higher in the combination group (P<0.05). Accordingly, it seems possible that cerebral ischemia may lead to more accumulated dopamine; meanwhile, most of the accumulated dopamine may be rapidly catabolited through a less energy consumed route and eventually to form more alternative metabolites other than DOPAC, 3-MT and HVA. In addition, EGb761 co-administrated with FK506 offers no more neuroprotective efficacy than EGb761used alone during cerebral ischemia.