Early administration of a second-generation perfluorochemical decreases ischemic brain damage in a model of permanent middle cerebral artery occlusion in the rat.
OBJECTIVE
Perfluorochemicals (PFCs) may exert a neuroprotective function in the early phase of ischemia by improving the oxygen supply to the endangered tissue. We have, therefore, investigated the effect of Oxycyte, a second-generation perfluorocarbon solution, on the extent of early ischemic brain damage in a model of permanent focal cerebral ischemia.


METHODS
Eight hours of permanent focal cerebral ischemia was induced in isoflurane anesthetized male Sprague-Dawley rats by unilateral middle cerebral artery (MCA) thread occlusion under the control of laser Doppler flowmetry (LDF). Animals were assigned to one of the following treatment groups: nO2-NaCl and hO2-NaCl-NaCl (0.9%, 1 ml/100 g i.v.) and nO2-Oxycyte and hO2-Oxycyte-Oxycyte (1 ml/100 g i.v.). The injection of NaCl or Oxycyte was performed immediately after MCA occlusion. After injection, breathing was changed to pure oxygen in groups hO2-NaCl and hO2-Oxycyte while animals in groups nO2-NaCl and nO2-Oxycyte were allowed to breathe air. The necrotic volume was calculated from serial coronal sections stained with silver-nitrate. In addition, nitrotyrosine production was studied by immunohistochemistry.


RESULTS
Upon MCA occlusion, animals showed a reduction of cerebral blood flow of approximately 80% of the LDF signal in all groups. Hemodynamic and metabolic parameters were not affected by the infusion of Oxycyte. The total infarct volume was reduced in hO2-Oxycyte animals [group nO2-NaCl: 341+/-31 mm3 (mean+/-SD), group hO2-NaCl: 351+/-33 mm3, group nO2-Oxycyte: 354+/-24 mm3, and group hO2-Oxycyte: 300+/-29 mm3, p < 0.05 versus all other groups]. Moreover, hO2-Oxycyte animals showed lesser intensity of nitrotyrosine staining when compared with hO2-NaCl animals.


CONCLUSIONS
These results suggest that Oxycyte administered immediately after the onset of vascular occlusion may exert neuroprotective effects in the early phase of brain ischemia.
Department of Neurosurgery, University Hospital Mannheim, Mannheim, Germany. johannes.woitzik@nch.ma.uni-heidelberg.de
Johannes
J
Woitzik
Nina
N
Weinzierl
Lothar
L
Schilling
D000704:Analysis of Variance; D000818:Animals; D001784:Blood Gas Analysis / Q000379:methods; D002545:Brain Ischemia / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005466:Fluorocarbons / Q000627:therapeutic use*; D007150:Immunohistochemistry / Q000379:methods; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000473:pathology; D017078:Laser-Doppler Flowmetry / Q000379:methods; D008297:Male; D009336:Necrosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010100:Oxygen / Q000627:therapeutic use*; D030421:Peroxynitrous Acid; D051381:Rats; D017207:Rats, Sprague-Dawley; D016622:Silver Staining / Q000379:methods; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D005466:Fluorocarbons; D018696:Neuroprotective Agents; D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D010100:Oxygen