Neutrophil inhibitory factor is neuroprotective after focal ischemia in rats.
We tested the neuroprotective potential of neutrophil inhibitory factor (rNIF), a novel 41-kd recombinant glycoprotein derived from a hookworm, in a model of focal cerebral ischemia in the rat. Male Wistar rats were assigned to treatment with rNIF and vehicle. Middle cerebral artery occlusion (MCAO) for 2 hours was induced by insertion of an intraluminal suture. Infusion of the drug was initiated at the onset of reperfusion. Infarct volume was determined 48 hours after reperfusion. Neutrophils were measured within the ischemic tissue by myeloperoxidase (MPO) staining. Treatment with rNIF resulted in a 48% reduction in cerebral infarction compared with control animals (p < 0.01). Neutrophil accumulation in the ischemic brains of rNIF-treated rats was reduced significantly (p < 0.01) compared with control animals. The number of neutrophils within the infarcted tissue correlated positively with the size of the area of infarction (p < 0.001, r = 0.6) within representative cerebral coronal sections. We demonstrated a significant neuroprotective effect of rNIF with continuous treatment for 48 hours following 2 hours of MCAO. The neuroprotective effect was correlated with a reduced number of neutrophils within the ischemic tissue. These results demonstrate potential therapeutic properties of rNIF in the management of stroke.
Department of Neurology, Henry Ford Health Science Center, Detroit, MI, USA.
N
N
Jiang
M
M
Moyle
H R
HR
Soule
W E
WE
Rote
M
M
Chopp
D000818:Animals; D001784:Blood Gas Analysis; D001835:Body Weight; D002545:Brain Ischemia / Q000188:drug therapy*; D006023:Glycoproteins / Q000097:blood / Q000494:pharmacology*; D015801:Helminth Proteins / Q000097:blood / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007958:Leukocyte Count; D008297:Male; D008565:Membrane Proteins; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009504:Neutrophils / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D015427:Reperfusion Injury / Q000188:drug therapy / Q000276:immunology; D013696:Temperature
D006023:Glycoproteins; D015801:Helminth Proteins; D008565:Membrane Proteins; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; C086581:NIF protein, Ancylostoma caninum