Neutrophil inhibitory factor treatment of focal cerebral ischemia in the rat.
The present study was designed to determine whether a hookworm-derived recombinant neutrophil inhibitory factor (rNIF) is neuroprotective when administered after initiation of focal cerebral ischemia in the rat. We measured the rNIF dose-response on cerebral infarct volume, the therapeutic time window, the therapeutic response to permanent ischemia, and whether rNIF treatment delays the maturation of the ischemic lesion (2 days), or reduces cerebral infarct volume at 7 days after middle cerebral artery occlusion (MCAO). MCAO was induced by an insertion of intraluminal 4-0 monofilament nylon suture into internal carotid artery (n=195). We demonstrate a significant neuroprotective effect of rNIF administration 48 h after MCAO in a dose-dependent fashion when treatment was initiated upon reperfusion after 2 h MCAO and maintained until 48 h after MCAO. The beneficial effect was lost under conditions of permanent MCAO. The therapeutic time window is 4 h after MCAO. Brief treatment (6 h) is not sufficient to provide protection for the final ischemic damage. Continuous treatment with a high dose of rNIF for a long duration (7 days) is necessary to achieve maximum neuroprotection.
Jiang
N
N
Henry Ford Health Sciences Center, Department of Neurology, Detroit, MI 48202, USA.
Chopp
M
M
Chahwala
S
S
D000818:Animals; D016466:CHO Cells; D002544:Cerebral Infarction / Q000473:pathology; D006224:Cricetinae; D006023:Glycoproteins / Q000627:therapeutic use*; D015801:Helminth Proteins / Q000627:therapeutic use*; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000627:therapeutic use
D006023:Glycoproteins; D015801:Helminth Proteins; D008565:Membrane Proteins; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; C086581:NIF protein, Ancylostoma caninum