Perfluorocarbon emulsions improve cognitive recovery after lateral fluid percussion brain injury in rats.
OBJECTIVE
Perfluorocarbon emulsions have been shown to improve outcomes in stroke models. This study examined the effect of Oxycyte, a third-generation perfluorocarbon emulsion (04RD33; Synthetic Blood International, Inc., Costa Mesa, CA) treatment on cognitive recovery and mitochondrial oxygen consumption after a moderate lateral fluid percussion injury (LFPI).


METHODS
Adult male Sprague-Dawley rats (Harlan Bioproducts for Science, Indianapolis, IN) were allocated to 4 groups: 1) LFPI treated with a lower dose of Oxycyte (4.5 mL/kg); 2) LFPI with a higher dose of Oxycyte (9.0 mL/kg); 3) LFPI with saline infusion; and 4) sham animals treated with saline. Fifteen minutes after receiving moderate LFPI or sham surgery, animals were infused intravenously with Oxycyte or saline within 30 minutes while breathing 100% O2. Animals breathed 100% O2 continuously for a total of 4 hours after injury. At 11 to 15 days after LFPI, animals were assessed for cognitive deficits using the Morris water maze test. They were sacrificed at Day 15 after injury for histology to assess hippocampal neuronal cell loss. In a parallel study, mitochondrial oxygen consumption values were measured by the Cartesian diver microrespirometer method.


RESULTS
We found that injured animals treated with a lower or higher dose of Oxycyte had significant improvement in cognitive function when compared with injured saline-control animals (P < 0.05). Moreover, injured animals that received either dose of Oxycyte had significantly less neuronal cell loss in the hippocampal CA3 region compared with saline-treated animals (P < 0.05). Furthermore, a lower dose of Oxycyte significantly improved mitochondrial oxygen consumption levels (P < 0.05).


CONCLUSIONS
The current study demonstrates that Oxycyte can improve cognitive recovery and reduce CA3 neuronal cell loss after traumatic brain injury in rats.
Zhou
Zhengwen
Z
Department of Neurosurgery, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia, USA.
Sun
Dong
D
Levasseur
Joseph E
JE
Merenda
Amedeo
A
Hamm
Robert J
RJ
Zhu
Jiepei
J
Spiess
Bruce D
BD
Bullock
M Ross
MR
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D002452:Cell Count; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D005466:Fluorocarbons / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010101:Oxygen Consumption / Q000187:drug effects; D010102:Oxygen Inhalation Therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D014949:Wounds, Nonpenetrating
D005466:Fluorocarbons; D018696:Neuroprotective Agents