NEUTROPHIL INHIBITORY FACTOR IS NEUROPROTECTIVE AFTER FOCAL ISCHEMIA IN RATS

We tested the neuroprotective potential of neutrophil inhibitory facto r (rNIF), a novel 41-kd recombinant glycoprotein derived from a hookwo rm, in a model of focal cerebral ischemia in the rat. Male Wistar rats were assigned to treatment with rNIF and vehicle. Middle cerebral art ery occlusion (MCAO) for 2 hours was induced by insertion of an intral uminal suture. Infusion of the drug was initiated at the onset of repe rfusion. Infarct volume was determined 48 hours after reperfusion. Neu trophils were measured within the ischemic tissue by myeloperoxidase ( MPG) staining. Treatment with rNIF resulted in a 48% reduction in cere bral infarction compared with control animals (P < 0.01). Neutrophil a ccumulation in the ischemic brains of rNIF-treated rats was reduced si gnificantly (p < 0.01) compared with control animals. The number of ne utrophils within the infaraed tissue correlated positively with the si ze of the area of infarction (p < 0.001, r = 0.6) within representativ e cerebral coronal sections. We demonstrated a significant neuroprotec tive effect of rNIF with continuous treatment for 48 hours following 2 hours of MCAO. The neuroprotective effect was correlated with a reduc ed number of neutrophils within the ischemic tissue. These results dem onstrate potential therapeutic properties of rNIF in the management of stroke.