Effect of carbon monoxide administration using haemoglobin-vesicles on the hippocampal tissue.

Abstract

Carbon monoxide (CO) is a toxic gas that causes neuropathy. However, CO is endogenously produced in small amounts showing various beneficial effects. We hypothesized that CO-bound haemoglobin-vesicle (HbV) administration would reduce cerebral ischaemia-reperfusion injury without causing neuropathy. Three experiments were conducted. First, rats were exposed to CO inhalation to create a CO-poisoning group, and they were sacrificed on 0, 7, 14, and 21 days after CO exposure. Histopathologically, hippocampal damage was prominent at 14 days. Second, the rats were administered with CO-HbV equivalent to 50 or 25% of circulating blood volume (CO-HbV50 or CO-HbV25 group). Rats were sacrificed 14 days after administration. Third, rats put into haemorrhagic shock by 50% of circulating blood withdrawal were resuscitated using saline, autologous blood, and CO-HbV. They were sacrificed 14 days after resuscitation. Hippocampal damage assessment clarified that almost no necrotic cells were observed in the CO-HbV50 group. Necrotic cells in the CO-HbV25 group were comparable to those found for the control group. In rats resuscitated from haemorrhagic shock, the hippocampal damage in the group using CO-HbV was the mildest. Administration of CO-HbV did not lead to marked hippocampal damage. Furthermore, CO-HbV was effective at preventing cerebral ischaemia-reperfusion injury after haemorrhagic shock.