%0 Journal Article %A Akira T. Kawaguchi %A Munetaka Haida %A Mariko Yamano %A Dai Fukumoto %A Yoshitaka Ogata %A Hideo Tsukada %T Liposome-Encapsulated Hemoglobin Ameliorates Ischemic Stroke in Nonhuman Primates: An Acute Study %D 2010 %R 10.1124/jpet.109.160051 %J Journal of Pharmacology and Experimental Therapeutics %P 429-436 %V 332 %N 2 %X An artificial oxygen carrier, liposome-encapsulated hemoglobin (LEH), protective in a rodent stroke model, was quantitatively evaluated in monkeys. Serial positron emission tomography studies using the steady-state 15O-gas inhalation method were performed to quantify O2 metabolism, which was compared based on the infarction extent and immunohistochemical evaluation in 19 monkeys undergoing middle cerebral artery occlusion (3 h), infusion of various LEH doses (n = 11), empty liposome (n = 4), or saline (n = 4) 5 min after the onset of ischemia, and reperfusion for 5 h. There was no significant difference in O2 metabolism until 3 h after reperfusion, when the cerebral metabolic rate of O2 (CMRO2) was significantly less suppressed in the cortex [mild suppression in CMRO2 (71–100%) of preischemic ipsilateral control as in the ischemic penumbra: 64.7 ± 14.3% in empty liposome versus 32.4 ± 7.9% in LEH (2 ml/kg) treatment, P < 0.05] but not in basal ganglia. Immunohistochemical studies showed a reciprocal expression of microtubular-associated protein II expression in the cortex and LEH deposition in basal ganglia, suggesting the LEH perfusion, but not deposition, afforded the protection. Dose-response studies revealed that as little as 0.4 ml/kg LEH (24 mg/kg hemoglobin) was effective in preserving CMRO2, whereas 2 and 10 ml/kg were protective in significantly reducing the area of infarction as well, by 66 and 56%, respectively, compared with animals receiving saline. CMRO2 and histological integrity were better preserved early after 3-h occlusion and reperfusion of the middle cerebral artery of monkeys receiving LEH early after onset of ischemia. Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics %U https://jpet.aspetjournals.org/content/jpet/332/2/429.full.pdf