Liposome‐Encapsulated Hemoglobin Ameliorates Ischemic Stroke in Nonhuman Primates: Longitudinal Observation

Abstract

Liposome-encapsulated hemoglobin (LEH) is protective early after brain ischemia in rats and nonhuman primates, but it remains unclear whether the protection persists and confers any benefits beyond the acute phase of brain ischemia and reperfusion. Ten monkeys underwent middle cerebral artery occlusion, received LEH (2 mL/kg, n = 5) or saline (2 mL/kg, n = 5) 5 min later, and reperfusion 3 h later. Positron emission tomography studies were repeated for the cerebral metabolic rate of O2 (CMRO2 ) as well as glucose (CMRglc) up to 8 days after reperfusion, when the animals were euthanized for morphological studies. There was no difference in O2 metabolism until 3 h after reperfusion, when CMRO2 was significantly better preserved in the cortex, but not in basal ganglia, on Day 0 in LEH-treated monkeys. The extent of cortical infarction (saline 68 ± 10% vs. LEH 38 ± 9%, P < 0.05) and CMRO2 (mild suppression: saline 34 ± 10% vs. LEH 14 ± 4%, P < 0.05) remained significantly better preserved 8 days later, when CMRglc showed a similar pattern of cortical protection (mild suppression: saline 49 ± 15% vs. LEH 37 ± 4%, P < 0.05) in LEH-treated monkeys, together with regained body weight. Somatic weight control, morphological integrity, CMRO2 , and CMRglc were better preserved immediately, as well as 8 days after occlusion and reperfusion of the middle cerebral artery in monkeys receiving LEH early after onset of ischemia.