Antineutrophil strategies

Neutrophil activation occurs in a variety of pathophysiologic scenarios that are neither strictly inflammatory nor infectious. Many of these events involve a relative or absolute ischemic state. Experimental studies have provided evidence for the role of activated neutrophils during ischemia and ischemia-reperfusion (I-R) injury in various organ systems, including the heart^1,2 and brain.^3-12 The hypothesis that activated neutrophils may exacerbate brain injury after I-R is supported by studies demonstrating that neutropenia^7,13-15 or inhibition of neutrophil function^6,9,10,16-18 can improve cerebral blood flow (CBF)^9,13,17 or reduce brain edema^7,10,18, and/or infarct size.^6,7,9,10,16

Although we have recently begun to understand the process of neutrophil migration and activation, the specific signal(s) that is responsible for activation or modulation remain unclear. Moreover, although experimental studies from our laboratory¹⁸ and others¹⁴ suggest that this activation occurs within the first hours after an ischemic event, the precise temporal profile in the human has received little attention. In the present studies, we have undertaken an examination of neutrophil activation in acute human cerebral ischemia and a novel approach toward modulating neutrophil activation.

Materials and Methods. All studies were approved by either the University of Vermont Institutional Review Board or the Institutional Animal Care and Use Committee.

Examination of neutrophil function in acute human stroke was initiated within 6 h of the ictus. Patients were excluded from the study if it was not possible to determine an accurate time frame for the stroke onset, if they had a rapidly resolving deficit consistent with a TIA, or if they ultimately had confirmation of another disease process. A total of 28 patients with acute stroke (15 bland, 13 with intracranial hemorrhage/hemorrhagic infarct) were entered into the study. Whole blood samples were taken at the time of the initial diagnosis (within 6 hours …