Objective
MCI-186 inhibits both nonenzymatic lipid peroxidation and lipid oxygenase pathway of the arachidonate cascade. This agent has several neuroprotective effects by inhibiting vascular endothelial cell injury and ameliorating neuronal damage in ischemic brain models. Clinically it is represents a neuroprotective efficacy and potentially useful for treating acute ischemic stroke, since it can exert significant effect on functional outcome as compared with placebo. However, to date, there is no assessment regarding any efficacy of MCI-186 based on the plasma biomarkers. Previously we first demonstrated that plasma oxidized low-density lipoprotein (OxLDL) reflects the brain oxidative damage in acute cerebral infarction. And also S100B levels in the plasma have been reported to correlate with the brain damage. The aim of this study is to investigate whether the efficacy of MCI-186 is reflected by the plasma biomarkers of brain damage.
Material and Methods
Our study population consisted of 43 patients (27 men and 16 women) who had suffered an ischemic cerebral infarct. Based on the location of the ischemic lesions, they were divided into two groups; G1(n=23) had cortical lesions, G2(n=20) lesions in the basal ganglia or brain stem. MCI-186 was administered for initial 14 days from admission for 26 patients (G1a, n=12, G2a, n=14). The initial use of the drug was within 6 h after the stroke onset. The efficacy was compared with patients not treated by MCI-186 (G1b, n=11, G2b, n=6). Plasma OxLDL was determined by a sandwich ELISA. S100B and MnSOD were measured using commercial kits. Neuronal deficits were evaluated by NIH stroke scale (NIHSS) on admission and discharge.
Results
In G1 group, admission plasma OxLDL was significantly higher than G2 group (p<0.01). The elevated plasma OxLDL in G1a on admission was significantly decreased after MCI-186 treatment (p<0.05). On the contrary, G1b patients had a persisted increase in plasma OxLDL until 3 days after the insult. Although there was significant difference between G1a and G1b on third days, both G2a and G2b patients had similar plasma OxLDL. The plasma level of S100B and MnSOD in G1a was significantly lower than in G1b 3 days after the treatment (p<0.05, respectively). NIHSS in G1a and G2a tended to be lower than in G1b and G2b, the difference was not significant.
Conclusions
This is the first evidence that indicated the efficacy of MCI-186 via plasma biomarkers. Our findings indicated that MCI-186 may be useful for the reduction of oxidative damage in the cortical infarction but not the other lesion, and suggested that this effect contributes to the decrease of brain damage, resulting in the decrease of S100B level.