title: Polynitroxyl albumin reduces infarct size in transient focal cerebral ischemia in the rat: potential mechanisms studied by magnetic resonance imaging.
abstract: Nitroxide free radicals are known to protect cells from oxidative damage. Diffusion-weighted and perfusion-weighted magnetic resonance imaging was used to evaluate the effects of polynitroxyl albumin (PNA) in a middle cerebral artery intraluminal suture model of transient focal cerebral ischemia in the rat. Three groups of Sprague-Dawley rats were investigated: (1) PNA (N=6), (2) human serum albumin (N =6), and (3) saline (N=7). The middle cerebral artery was occluded for 2 hours. Treatment was started 30 minutes after induction of ischemia. A total dose of 1% body weight (volume/weight) of PNA (23.5 mg/dL protein and 110 mmol/L nitroxide), albumin (23.5 mg/dL), or saline was injected intravenously at three time points: 0.5% at 0.5 hours, 0.25% at 2 hours (i.e., just before reperfusion), and 0.25% at 4 hours after occlusion. Six sets of diffusion- and perfusion-weighted magnetic resonance images were acquired throughout the 2 hours of ischemia and the 2 hours of reperfusion. The rats were killed at 24 hours, and the brains were stained with 2,3,5-triphenyltetrazolium chloride (TTC). Diffusion-weighted imaging showed that the growth of the ischemic lesion was suppressed in the PNA-treated group. The 4 hours diffusion-weighted imaging--derived hemispheric lesion volume in the PNA-treated group (25%+/-9%) was significantly smaller than that in the saline-treated (43%+/-13%; P=0.016) or albumin-treated groups (38%+/-6%; P=0.017). A larger difference was observed for the 24-hour TTC-derived lesion volumes in the PNA (8%+/-7%), saline (35%+/-8%; P < 0.001), and albumin (31%+/-6%; P < 0.001) groups. Perfusion-weighted imaging demonstrated a marked improvement in cerebral perfusion in the PNA-treated group during ischemia and reperfusion. In conclusion, treatment with PNA results in an improvement in perfusion and a reduction of infarct volume in a model of transient focal cerebral ischemia in the rat.
authors.affiliation: Department of Radiology, Stanford University, California 94305-5488, USA.
authors.forename: C
authors.initials: C
authors.lastname: Beaulieu
authors.forename: E
authors.initials: E
authors.lastname: Busch
authors.forename: J
authors.initials: J
authors.lastname: Röther
authors.forename: A
authors.initials: A
authors.lastname: de Crespigny
authors.forename: C J
authors.initials: CJ
authors.lastname: Hsia
authors.forename: M E
authors.initials: ME
authors.lastname: Moseley
mesh_terms: D000818:Animals; D002544:Cerebral Infarction / Q000188:drug therapy*; D002546:Ischemic Attack, Transient / Q000188:drug therapy*; D008279:Magnetic Resonance Imaging; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000627:therapeutic use
chemical_list: D018696:Neuroprotective Agents; D012709:Serum Albumin