The development of cerebral infarction after transient ischemia is attributed to postischemic delayed hypoperfusion in the microvascular region. In the present study, we assessed the microvascular perfusion capacity of infused liposome-encapsulated hemoglobin (LEH) in a therapeutic approach for transient middle cerebral artery occlusion (tMCAO).
Two-hour middle cerebral artery occlusion rats were immediately subjected to intra-arterial infusion of LEH (LEH group) or saline (vehicle group) or no treatment (control group), and then to recanalization. Neurological findings, infarct and edema progression, microvascular endothelial dysfunction, and inflammatory reactions were compared between the 3 groups after 24 hours of reperfusion. Microvascular perfusion in the early phase of reperfusion was evaluated by hemoglobin immunohistochemistry and transmission electron microscopy.
The LEH group achieved significantly better results in all items evaluated than the other groups. Hemoglobin immunohistochemistry revealed that the number of hemoglobin-positive microvessels was significantly greater in the LEH group than in the other groups (P < .01), with microvascular perfusion being more likely in narrow microvessels (≤5 µm in diameter). An electron microscopic examination revealed that microvessels in the control group were compressed and narrowed by swollen astrocyte end-feet, whereas those in the LEH group had a less deformed appearance and contained LEH particles and erythrocytes.
The results of the present study demonstrated that the infusion of LEH reduced infarctions after tMCAO with more hemoglobin-positive and less deformed microvessels at the early phase of reperfusion, suggesting that the superiority of the microvascular perfusion of LEH mediates its neuroprotective effects.
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- Recanalization and reperfusion therapies for acute ischemic stroke.Cerebrovasc Dis. 2009; 27: 162-167
- Capillary flow and diameter changes during reperfusion after global cerebral ischemia studied by intravital video microscopy.J Cereb Blood Flow Metab. 2004; 24: 383-391
- Temporary focal cerebral ischemia results in swollen astrocytic end-feet that compress microvessels and lead to delayed focal cortical infarction.J Cereb Blood Flow Metab. 2011; 31: 328-338
- Transarterial regional brain hypothermia inhibits acute aquaporin-4 surge and sequential microvascular events in ischemia/reperfusion injury.Neurosurgery. 2016; 79: 125-134
- Liposome-encapsulated hemoglobin, trm-645: current status of the development and important issues for clinical application.Artif Organs. 2009; 33: 146-152
- Liposome-encapsulated hemoglobin ameliorates impairment of fear memory and hippocampal dysfunction after cerebral ischemia in rats.J Pharmacol Sci. 2010; 114: 409-419
- Therapeutic potentials of an artificial oxygen-carrier, liposome-encapsulated hemoglobin, for ischemia/reperfusion-induced cerebral dysfunction in rats.J Pharmacol Sci. 2010; 114: 189-197
- Efficacy of liposome-encapsulated hemoglobin in a rat model of cerebral ischemia.Artif Organs. 2014; 38: 650-655
- Liposome-encapsulated hemoglobin reduces the size of cerebral infarction in the rat: evaluation with photochemically induced thrombosis of the middle cerebral artery.Stroke. 2007; 38: 1626-1632
- Liposome-encapsulated hemoglobin ameliorates ischemic stroke in nonhuman primates: longitudinal observation.Artif Organs. 2013; 37: 904-912
- Liposome-encapsulated hemoglobin ameliorates ischemic stroke in nonhuman primates: an acute study.J Pharmacol Exp Ther. 2010; 332: 429-436
- In vivo distribution of liposome-encapsulated hemoglobin determined by positron emission tomography.Artif Organs. 2009; 33: 164-168
- Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat. Effects of neutrophil depletion.Stroke. 1994; 25: 1469-1475
- Post-ischemic intra-arterial infusion of liposome-encapsulated hemoglobin can reduce ischemia reperfusion injury.Brain Res. 2014; 1554: 59-66
- Reversible middle cerebral artery occlusion without craniectomy in rats.Stroke. 1989; 20: 84-91
- Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats. Statistical validation.Stroke. 1995; 26: 627-634
- Hyperbaric oxygen-induced attenuation of hemorrhagic transformation after experimental focal transient cerebral ischemia.Stroke. 2007; 38: 1362-1367
- RBC velocities in single capillaries of mouse and rat brains are the same, despite 10-fold difference in body size.Brain Res. 2010; 1320: 69-73
- Mannitol infusion immediately after reperfusion suppresses the development of focal cortical infarction after temporary cerebral ischemia in gerbils.Neuropathology. 2014; 34: 360-369
- Brain microvessels: factors altering their patency after the occlusion of a middle cerebral artery (Wistar rat).Am J Pathol. 1994; 145: 728-740
- Mild intraischemic hypothermia reduces postischemic hyperperfusion, delayed postischemic hypoperfusion, blood-brain barrier disruption, brain edema, and neuronal damage volume after temporary focal cerebral ischemia in rats.J Cereb Blood Flow Metab. 1994; 14: 620-627
- Secondary deterioration of apparent diffusion coefficient after 1-hour transient focal cerebral ischemia in rats.J Cereb Blood Flow Metab. 2000; 20: 1474-1482
- Inflammatory mechanisms in ischemic stroke: role of inflammatory cells.J Leukoc Biol. 2010; 87: 779-789
- Matrix metalloproteinases and blood-brain barrier disruption in acute ischemic stroke.Front Neurol. 2013; 4: 32
- Transient increase of cytokine-induced neutrophil chemoattractant, a member of the interleukin-8 family, in ischemic brain areas after focal ischemia in rats.Stroke. 1995; 26: 318-322
- Changes in oxidative stress, iNOS activity and neutrophil infiltration in severe transient focal cerebral ischemia in rats.Brain Res. 2002; 958: 166-175
Published online: August 23, 2017
Accepted: July 25, 2017
Received in revised form: July 20, 2017
Received: May 18, 2017
© 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.