ZINC PROTOPORPHYRIN, ZINC ION, AND PROTOPORPHYRIN REDUCE FOCAL CEREBRAL-ISCHEMIA

Background and Purpose Zinc protoporphyrin pretreatment protects again st temporary focal ischemic brain injury in rats. However, it is not k nown whether the zinc or the protoporphyrin portion of zinc protoporph yrin has effects on focal cerebral ischemia. Hence, all three agents w ere compared with regard to infarct size and edema in a rat model of m iddle cerebral artery occlusion. Methods Four groups of adult male Spr ague-Dawley rats were subjected to 2 hours of temporary middle cerebra l artery occlusion followed by 22 hours of reperfusion. Each group was pretreated 30 minutes before middle cerebral artery occlusion with 0. 9% NaCl, and then three groups were given equimolar doses of zinc prot oporphyrin, zinc chloride, or protoporphyrin, respectively. Regional c erebral blood flow in the ischemic cortex was monitored with a laser D oppler flowmeter. Cerebral infarct size, brain water content, and ion content were measured 24 hours after the onset of occlusion. Results R egional cerebral blood flow during middle cerebral artery occlusion wa s approximately 9.2% to 13% of baseline in all four groups. Brain wate r content in the infarcted zone after temporary focal ischemia in cont rol, zinc protoporphyrin, zinc chloride, and protoporphyrin groups was 85.7%, 80.6%, 85.6%, and 81.4%, respectively. Brain sodium content in the same areas in all four groups paralleled the water content. Infar ct size in the controls and groups treated with zinc protoporphyrin, z inc, and protoporphyrin was 25.6%, 7.2%, 7.6%, and 7.2%, respectively. Compared with the control group, the infarct volume in all three trea ted groups was significantly reduced (P<.05). Conclusions The present results indicate that zinc protoporphyrin, but also zinc and protoporp hyrin, contribute to brain-protective effects when administered early in a temporary focal ischemia model. Zinc chloride reduced infarct siz e but not edema formation when compared with zinc protoporphyrin and p rotoporphyrin. Zinc ion in vivo has brain-protective effects, confirmi ng in vitro studies previously reported by some but contrary to report s of others. Blood versus brain neuropil and cell body concentrations of zinc ion need to be studied in the future to define the precise rol e of zinc in the complex mechanisms involved in brain ischemia.