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 ischemic injury in two rat models of focal ischemia was investigated. In Experiment I, a model of focal ischemia with partial reperfusion was used. Although significant and discrete ischemic damage within the neocortex was nearly maximal at 12 h postocclusion, no elevation in neutrophils was seen at this time point. Even after 21 h postocclusion, only a subtle increase in neutrophils within the ischemic tissue was observed. To further investigate the possible role of neutrophils in cerebral ischemia, the effect of cyclophosphamide-induced neutropenia was investigated (Experiment II). While a marked reduction (>98%) in systemic neutrophils was achieved in advance of and during the ischemic challenge, no reduction in the volume of ischemic damage was observed. In Experiment III, variations in the rat model of focal ischemia were made to produce a larger area of ischemic damage, as well as to permit; complete 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 conditions of partial, as well as complete, reperfusion. Moreover, at the time points when elevations in neutrophils were observed, no further increase in volume of ischemic damage was noted. Finally, pharmacologic removal of neutrophils prior to ischemia did not alter the size of the ischemic region. These data therefore fail to support the hypothesis that neutrophils play a general and essential role in infarct formation following focal brain ischemia and argue that further studies are required to more clearly elucidate the conditions under which neutrophils might participate in ischemic pathogenesis. (C) 1996 Academic Press, Inc.