Trace element, antioxidant activity, and lipid peroxidation levels in brain cortex of gerbils after cerebral ischemic injury.

Proper trace element level and antioxidant enzyme activity are crucial for the brain in maintaining normal neurological functions. To our knowledge, alteration of lipid peroxidation status, trace element level, and antioxidant activity in the homogenates of brain cortex after cerebral ischemia in gerbil, however, has not been investigated so far. Male Mongolian gerbils were divided into control and ischemic subjects. Cerebral ischemia was induced by occlusion of the right middle cerebral artery and right common carotid artery for 1 h. Experimental results showed that a significant increase (P < 0.01) of the malondialdehyde level was found in the ischemic brain as compared with the control group. Trace element analysis indicated that a remarkable elevation (P < 0.01) of the level of iron (Fe), chromium (Cr), and a statistical decrease of selenium (Se) and zinc (Zn) (P < 0.05) concentration were observed in the ischemic brain as compared with the control subject. No significant change (P > 0.05) of the copper (Cu) level was found in both experimental groups. Additionally, antioxidant activity of superoxide dismutase (P < 0.01) and catalase (P < 0.05) was significantly decreased in the ischemic brain as compared with the control subject. Taking all results together, it is conceivable to manifest the experimental findings that cerebral ischemia not only may result in an enhanced oxidative stress but also may lead to further oxidative injury. Moreover, disturbance of trace element level combined with declined antioxidant activity seems to play a significant role in responsible for the etiology of cerebral ischemia.

Ginkgo biloba leaf extract (EGb761) combined with neuroprotective agents reduces the infarct volumes of gerbil ischemic brain.

Ginkgo biloba exerts many pharmacological actions. It possesses antioxidant properties, the ability of neurotransmitter/receptor modulation and antiplatelet activation factor. This research is designed to investigate the neuroprotective effects of long-term treatment with EGb761 (a standard form of the extract of Ginkgo biloba leaf) in combination with MgSO(4), FK506, or MK-801 on the infarct volume of male gerbils' brain induced by unilateral middle cerebral artery occlusion (MCAO). Thirty-five gerbils fed a standard diet were intragastrically given water or EGb761 (100 mg/kg/day) for one week. Five randomized groups were established: control (n = 7), EGb761 (n = 8), EGb761 + MgSO(4) (n = 7), EGb761 + FK506 (n = 7), and EGb761 + MK-801 (n = 6). The three drug-combination groups were injected with MgSO(4) (90 mg/kg), FK506 (0.5 mg/kg), or MK-801 (1 mg/kg), respectively 30 min before MCAO. Gerbils were anesthetized and craniectomized to expose the right middle cerebral artery (MCA). The right MCA was constricted with an 8-0 suture to produce a permanent ligation for 24 hours. Postmortem infarct volumes were determined by quantitative image analysis of 2,3,5-triphenyltetrazolium chloride (TTC)-stained brain sections. Results showed that the total infarct volumes of the four treated groups either EGb761 alone or in combination with drugs were lower than the control group by 36.1% (EGb761 alone), 40.3% (EGb761 + MgSO(4)), 35.3% (EGb761 + FK506), and 56.4% (EGb761 + MK-801), respectively (p < 0.01). The main affected areas of the brain in the four treated groups were significantly focused between 4 and 6 mm from the frontal pole, when compared to the control group (p < 0.01). All animals in the five groups had infarctions in both cortex and subcortex. These results indicate that long-term pre-treatment of EGb761 administered either alone or in combination with drugs significantly effective neuroprotection on infarct volume in gerbil ischemic brains.

Ginkgo biloba extract (EGb761) and FK506 preserve energy metabolites in the striatum during focal cerebral ischemia and reperfusion in gerbils monitored by microdialysis.

Cell death after cerebral ischemia is mediated by the accumulation of excitatory amino acids, calcium influx into cells and the generation of free radicals. The aim of this study was to evaluate changes in energy-related metabolites in the striatum of gerbils subjected to focal cerebral ischemia after pretreatment with Ginkgo biloba extract (EGb761), a well-known antioxidant, and FK506, a calcium-dependent phosphatase calcineurin inhibitor. Ischemia was induced by occlusion of the right common carotid artery and the right middle cerebral artery for 60 min. A microdialysis probe was inserted into the right striatum to monitor extracellular glucose, lactate and pyruvate levels. This study showed decreases in glucose (10% of the baseline), pyruvate (20% of the baseline) and lactate (60% of the baseline), and a 5-fold increase in the lactate to pyruvate ratio during ischemia in the control group. Both EGb761 treatment and the combination (EGb761 and FK506) therapy significantly preserved glucose (50% of the baseline) and pyruvate (60% of the baseline) levels during ischemia. The marked increase in the lactate to pyruvate ratio was not observed in the combination group. These results suggest that preservation of cellular energy metabolism during cerebral ischemia and after restoration with reperfusion may contribute to the neuroprotective effects of EGb761 and FK506.

Effect of one week treatment with Ginkgo biloba extract (EGb761) on ischemia-induced infarct volume in gerbils.

The present study was designed to evaluate the neuroprotective effects of Ginkgo biloba leaf extract (EGb761) in male gerbils subjected to focal cerebral ischemia produced by permanent occlusion of the right middle cerebral artery. In this study, gerbils were fed standard chow with or without EGb761 (100 mg/kg/day, i.g.) prior to cerebral ischemia for 1 week. Gerbils were anesthetized and craniectomized to expose the right middle cerebral artery (MCA). The right MCA was constricted with an 8-0 suture to produce a permanent ligation. Infarct volume was assessed by TTC (2,3,5-triphenyl-tetrazolium chloride) staining 24 hours after initiation of cerebral ischemia. Results showed that the EGb761 group had significant reduction of infarct volume 4 and 6 mm from the frontal pole by 40% and 30%, respectively when compared to the control group (p < 0.05). Mean locomotor activity of gerbils was reduced 24 hours after the occlusion of the MCA in both groups. However, there was no difference in locomotor activity between groups either 30 minutes before or 24 hours after the occlusion (p > 0.05).