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Effect of carbon monoxide administration using haemoglobin-vesicles on the hippocampal tissue
Chie Okuda1,2, Hiromi Sakai1
1Department of Chemistry, Nara Medical University, Kashihara, Japan.
Insights
Carbon monoxide-bound hemoglobin-vesicles (CO-HbV) effectively reduced brain damage from ischemia-reperfusion injury. This CO-HbV administration showed no signs of neuropathy, unlike carbon monoxide gas exposure.
Area of Science:
- Biomedical Engineering
- Toxicology
- Neuroscience
Background:
- Carbon monoxide (CO) is a toxic gas causing neuropathy, but endogenous CO has beneficial effects.
- Carbon monoxide-bound hemoglobin-vesicles (CO-HbV) are a potential therapeutic agent.
- Cerebral ischemia-reperfusion injury is a significant clinical concern.
Purpose of the Study:
- To investigate the neuroprotective effects of CO-HbV against cerebral ischemia-reperfusion injury.
- To assess whether CO-HbV administration causes neuropathy.
- To evaluate CO-HbV efficacy in a rat model of hemorrhagic shock and resuscitation.
Main Methods:
- Rats exposed to CO inhalation to assess toxicity and neuropathology.
- Rats administered with varying volumes of CO-HbV (50% or 25% blood volume).
- Rats subjected to hemorrhagic shock, resuscitated with saline, autologous blood, or CO-HbV, followed by hippocampal damage assessment.
Main Results:
- CO inhalation caused significant hippocampal damage by day 14.
- CO-HbV administration (50%) resulted in minimal hippocampal damage.
- CO-HbV resuscitation from hemorrhagic shock showed the mildest hippocampal injury compared to saline or autologous blood.
Conclusions:
- CO-HbV administration is effective in preventing cerebral ischemia-reperfusion injury.
- CO-HbV shows therapeutic potential without inducing neuropathy.
- CO-HbV represents a promising treatment for conditions involving cerebral ischemia-reperfusion.
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.
