Zinc Protoporphyrin, Zinc Ion, and Protoporphyrin Reduce Focal Cerebral Ischemia

Abstract

Background and Purpose Zinc protoporphyrin pretreatment protects against temporary focal ischemic brain injury in rats. However, it is not known whether the zinc or the protoporphyrin portion of zinc protoporphyrin has effects on focal cerebral ischemia. Hence, all three agents were compared with regard to infarct size and edema in a rat model of middle cerebral artery occlusion. Methods Four groups of adult male Sprague-Dawley rats were subjected to 2 hours of temporary middle cerebral 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 protoporphyrin, zinc chloride, or protoporphyrin, respectively. Regional cerebral blood flow in the ischemic cortex was monitored with a laser Doppler flowmeter. Cerebral infarct size, brain water content, and ion content were measured 24 hours after the onset of occlusion. Results Regional cerebral blood flow during middle cerebral artery occlusion was approximately 9.2% to 13% of baseline in all four groups. Brain water content in the infarcted zone after temporary focal ischemia in control, 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. Infarct size in the controls and groups treated with zinc protoporphyrin, zinc, and protoporphyrin was 25.6%, 7.2%, 7.6%, and 7.2%, respectively. Compared with the control group, the infarct volume in all three treated groups was significantly reduced ( P <.05). Conclusions The present results indicate that zinc protoporphyrin, but also zinc and protoporphyrin, contribute to brain-protective effects when administered early in a temporary focal ischemia model. Zinc chloride reduced infarct size but not edema formation when compared with zinc protoporphyrin and protoporphyrin. Zinc ion in vivo has brain-protective effects, confirming in vitro studies previously reported by some but contrary to reports of others. Blood versus brain neuropil and cell body concentrations of zinc ion need to be studied in the future to define the precise role of zinc in the complex mechanisms involved in brain ischemia.