Synergistic efficacy of magnesium sulfate and FK506 on cerebral ischemia-induced infarct volume in gerbil.

BACKGROUND

In this study, we administered intraperitoneal magnesium sulfate (90 mg/kg), either alone or in combination with FK506 (0.5 mg/kg) in order to investigate the neuroprotective synergetic effects of both, 30 min before permanent occlusion of the middle cerebral artery (MCA) in gerbil.

MATERIAL/METHODS: Postmortem infarct volume was determined by quantitative image analysis of triphenyltetrazolium-stained brain sections, collected at 1 h, 3 h and 24 h after initiation of cerebral ischemia, to measure consistent infarct volumes of the post -ischemic gerbil brain. Twenty-four male gerbils were intraperitoneally injected with MgSO4 (n=7), FK506 (n=8), or MgSO4 +FK506 (n=9), 30 min before permanent MCA occlusion. The brains of the treated groups were stained at 24 h after initiation of cerebral ischemia.

RESULTS

Significant and consistent infarct volumes (78.3 +/- 3.6 mm3) were observed in the 24 H control group. The infarct volume in the MgSO4 + FK506 group was significantly reduced at each slice, compared to the untreated 24 H control group (P<0.05). Magnesium sulfate reduced total infarct volume by 25.4% (P<0.05), FK506 by 41% (P<0.05), and MgSO4 +FK506 by 50.5% (P<0.05). Also, the infarct volume (38.7 +/- 5.2 mm3) in the MgSO4 + FK506 group was the smallest in all the treated groups, near the volumes seen in the untreated 3H group.

CONCLUSIONS

Acute administration of a combination of MgSO4 and FK506 has a synergetic efficacy against brain damage by permanent focal cerebral ischemia.