Article
Two-dose evaluation of efficacy and safety of perfluorocarbon Oxycyte™ in diffuse traumatic brain injury in the rat
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Published: | September 16, 2010 |
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Objective: Approximately 1/3 of severe brain injury patients show reduced brain oxygen tension (<25 mmHg) often due to reduced cerebral blood flow, during the first 24 hours following injury, leading to post-traumatic brain damage and a worse outcome. These secondary insults include hypoxia, ischemia, excitotoxicity, apoptosis, and metabolic failure. Neuronal tissue especially hippocampal areas of CA1/CA3 and dentate gyrus are extremely vulnerable to several types of secondary insults. Reperfusion after ischemia may be associated with inflammation and oxidative stress leading to the so called reperfusion injury. During hypoxia/ischemia, improvement of oxygen delivery may be of therapeutic benefit to ameliorate the damage associated with reperfusion. One way to increase oxygen delivery is by augmentation of dissolved oxygen in the blood by using perfluorocarbons (PFC).
Methods: In our study we examined the effect of administration of PFC, a third-generation perfluorocarbon on brain tissue oxygenation and histological damage after a moderate lateral fluid percussion injury (LFPI) followed by a delayed hypoxic insult. In our studies adult male Sprague-Dawley rats were allocated to 2 different groups: Group-1: LFPI treated with 9mL/kg i.v. Oxycyte™ versus Intralipid control, 10 min post-injury. The following day a second administration of the Oxycyte™ versus Intralipid (9mL/kg i.v.) was combined with a 30 minute hypoxic phase. Brain tissue oxygenation was measured by a Licox® probe placed in the damaged area during hypoxia and reperfusion. In a second group of animals the histological damage in hippocampal neuronal cell count was assessed.
Results: Results of our acute experiments indicated higher oxygenation levels in the brain tissue of PFC treated rats within the hypoxic period as compared to controls. In the reperfusion phase of the experiment, control animals showed higher oxygen levels during reperfusion, whereas PFC treated animals achieved pre-hypoxic oxygen levels. Hippocampal neuronal cell count showed higher amount of survived cells in the PFC group compared to the control group.
Conclusions: Taken together, these data show that PFC improves oxygen delivery to brain tissue in hypoxic conditions after traumatic brain injury in rats and seems to protect damaged neuronal cells within the hippocampus. Both doses of PFC appear safe, and therefore might reduce secondary hypoxic /ischemic damage, after TBI.