Polyhemoglobin-superoxide dismutase-catalase blood substitute for ichemia-reperfusion in brain.

摘要

Cerebrovascular disease, as manifested by stroke, is the most common acute neurological illness in the North America. The ischemic insult results in an interruption of blood flow to the central nervous system (CNS). Transient global cerebral ischemia-reperfusion is known to cause disruption of the blood-brain-barrier (BBB) and edema formation. Past investigations have indicated that following reperfusion, oxygen free radicals, superoxide in particular, are formed and played a major role in the development of neurological disorders and brain dysfunctions. The present first generation blood substitute consisting of a cross-linked hemoglobin (PolyHb) solution is useful for perfusing obstructed regions of vessels; however, this solution is not able to scavenge reactive oxygen radicals.; Since our newly developed second-generation hemoglobin-based blood substitute, PolyHb cross-linked with superoxide dismutase and catalase (PolyHb-SOD-CAT), has the ability to scavenge reactive oxygen radicals, we hypothesize that this oxygen-carrying agent is able to deliver the required oxygen to brain tissue and remove the harmful oxygen free radicals in the same instance. In this investigation, we compare the physiological effects of this formulation with that of the first-generation hemoglobin-based blood substitute (PolyHb) on rat brain tissue using a 60-minutes transient global ischemia-reperfusion rat brain model.; Comparative molecular distribution was performed to observe the cross-linking process. Verifications of superoxide dismutase (SOD) and catalase (CAT) activity and oxygen-carrying property of PolyHb-SOD-CAT were also conducted. Tracking of cerebral water contents and colorimetric assay of Evans blue influx into brain tissue were used to evaluate the integrity of the blood-brain-barrier (BBB). This study shows that PolyHb-SOD-CAT can supply oxygen to ischemic tissues without causing reperfusion injury in a global stroke model.