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.
Woitzik
Johannes
J
Department of Neurosurgery, University Hospital Mannheim, Mannheim, Germany. johannes.woitzik@nch.ma.uni-heidelberg.de
Weinzierl
Nina
N
Schilling
Lothar
L
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