LACK OF EVIDENCE FOR NEUTROPHIL PARTICIPATION DURING INFARCT FORMATION FOLLOWING FOCAL CEREBRAL-ISCHEMIA IN THE RAT

The involvement of neutrophils in the pathogenesis of cerebral ischemi c injury in two rat models of focal ischemia was investigated. In Expe riment I, a model of focal ischemia with partial reperfusion was used. Although significant and discrete ischemic damage within the neocorte x was nearly maximal at 12 h postocclusion, no elevation in neutrophil s was seen at this time point. Even after 21 h postocclusion, only a s ubtle increase in neutrophils within the ischemic tissue was observed. To further investigate the possible role of neutrophils in cerebral i schemia, the effect of cyclophosphamide-induced neutropenia was invest igated (Experiment II). While a marked reduction (>98%) in systemic ne utrophils was achieved in advance of and during the ischemic challenge , no reduction in the volume of ischemic damage was observed. In Exper iment III, variations in the rat model of focal ischemia were made to produce a larger area of ischemic damage, as well as to permit; comple te reperfusion of blood to the affected cortex. While more neutrophils were seen in this variation of the model, very few were observed (<1 per field) prior to the time that maximal ischemic damage had already occurred. Together, these experiments revealed that substantial brain necrosis occurred prior to the appearance of neutrophils, under condit ions of partial, as well as complete, reperfusion. Moreover, at the ti me points when elevations in neutrophils were observed, no further inc rease in volume of ischemic damage was noted. Finally, pharmacologic r emoval of neutrophils prior to ischemia did not alter the size of the ischemic region. These data therefore fail to support the hypothesis t hat neutrophils play a general and essential role in infarct formation following focal brain ischemia and argue that further studies are req uired to more clearly elucidate the conditions under which neutrophils might participate in ischemic pathogenesis. (C) 1996 Academic Press, Inc.