Liposome‐Encapsulated Hemoglobin Alleviates Hearing Loss After Transient Cochlear Ischemia and Reperfusion in the Gerbil

Okada, Masahiro; Kawaguchi, Akira T.; Hakuba, Nobuhiro; Takeda, Sadanori; Hyodo, Jun; Imai, Katsunori; Hato, Naohito; Gyo, Kiyofumi

doi:10.1111/j.1525-1594.2011.01306.x

Cited by 23 publications

(42 citation statements)

References 25 publications

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“…These observations of whole‐brain I/R showed that l ‐LEH was protective in SAT performance and amygdala morphology but not in the Morris water maze task and CA1 cellularity in the hippocampus. Although these observations may appear contradictory, they might be compatible with our previous observations on focal brain ischemia, where LEH was protective largely in the cortex but not as much in the basal ganglia . Such observation may also be compatible with the results of Hamadate , who demonstrated the benefits of l ‐LEH treatment in a four‐vessel occlusion model in the rat.…”

Section: Discussionsupporting

confidence: 90%

“…Benefits of LEH in focal brain ischemia were mainly in the cortex and amygdala but not so much in the basal ganglia and hippocampus, suggesting possible difference(s) in perfusion patterns during ischemia and oxidative stress at reperfusion. In the current study, we examined the effect(s) of l ‐LEH on global and complete brain ischemia, as there could be differences from focal ischemia with regard to the role of collaterals and the severity of reperfusion injury.…”

Section: Discussionmentioning

confidence: 95%

“…Briefly, it is a liposome capsule measuring 250 nm in mean diameter, containing hemoglobin eluted from donated human RBCs outdated for transfusion. The liposome capsule is coated with polyethylene glycol to reduce aggregation and capture by the reticuloendothelial system, allowing its prolongation of circulation half‐life to 13 h in the rodent and to 70 h in nonhuman primates . Inositol hexaphosphate was included as an allosteric effector to reduce O 2 affinity to a lower level ( l ‐LEH, P 50 O 2 = 45 mm Hg) than that of rodent RBCs (P 50 O 2 = 30 mm Hg) in the current study.…”

Section: Methodsmentioning

confidence: 99%

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Effects of Liposome-Encapsulated Hemoglobin on Learning Ability in Tokai High-Avoider Rat After Total Brain Ischemia and Reperfusion

et al. 2014

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Liposome-encapsulated hemoglobin with low O2 -affinity (l-LEH) was shown to be protective in focal brain ischemia and reperfusion (I/R) in rats and primates. We tested l-LEH in the transient whole brain ischemia in the Tokai high-avoider rat (THA), which has been selected, mated, and bred over 77 generations for a high and consistent learning ability determined by the Sidman avoidance test (SAT). Young/naïve (before SAT) and adult/parent (after SAT) THA rats underwent acute and complete four-vessel occlusion in the chest for 3 or 5 min, administration of 2 mL/kg of l-LEH, saline, or homologous washed red blood cells (RBCs), reperfusion, and resuscitation. One week later, all rats underwent SAT, open-field behavioral observation, Morris water maze tests, and morphological study. Whereas young/naïve rats treated with l-LEH retained a rapid and consistent learning curve as in nonischemic controls, THA rats treated with RBCs or saline had retarded learning response on SAT as well as reduced cellularity in the amygdala. Adult/parent rats with established memory on SAT maintained perfect achievement even after I/R. In contrast, l-LEH-treated rats showed no better performance on Morris water maze (function) or cellularity of the CA1 sector of the hippocampus (morphology) compared with the rats treated with RBCs. Although task performance on SAT and Morris water maze appeared antithetical, morphological observations corresponded to the respective functions, suggesting that l-LEH was protective only for the amygdala on SAT tasks but not for the CA1 sector of the hippocampus on spatial orientation as in our previous studies on focal brain I/R, where the cortex was preserved better than basal ganglia.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 95%

Section: Methodsmentioning

confidence: 99%

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Effects of Liposome-Encapsulated Hemoglobin on Learning Ability in Tokai High-Avoider Rat After Total Brain Ischemia and Reperfusion

et al. 2014

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“…However, h ‐LEH has been reported to be more efficient, equally benefiting with 1/5 to 1/25 dosage, than l ‐LEH in cerebral ischemia/reperfusion . Similar results are observed in cochlear ischemia/reperfusion , where it is more protective of hearing in the order of h ‐LEH, l ‐LEH, and saline or RBC. Thus, both the particle size and O 2 ‐affinity appear to be involved in O 2 delivery and aerobic metabolism.…”

Section: Discussionmentioning

confidence: 57%

Effects of Liposome-Encapsulated Hemoglobin on Gastric Wound Healing in the Rat

et al. 2014

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Liposome-encapsulated hemoglobin (LEH) may improve microcirculation and oxygen (O2 ) metabolism at a surgical wound to accelerate its healing. Ten mL/kg of LEH with high (h-LEH) or low O2 -affinity (l-LEH), homologous red blood cells (RBC), empty liposome or saline as a control was infused before a 10-mm incision and interrupted suture closure of the gastric wall in a total of 110 rats. Two and 4 days later, the stomach was excised for bursting pressure determination and histological sampling. The dose-response relationship was examined in 70 additional rats receiving progressively reduced doses of h-LEH. Hypoxia-inducible factor-1α (HIF-1α) was stained immunohistochemically in 54 other rats to examine its accumulation at the anastomotic sites. Bursting pressure of the surgical wound was significantly higher 2 days after surgery only in the h-LEH-treated rats (P < 0.05), but not at 4 days after surgery, when other rats showed increased bursting pressure to a nonsignificant level. Histological examination revealed less granulocyte infiltration, better granulation, and more macrophage infiltration in h-LEH-treated rats at 2 days, but no longer at 4 days postsurgery. Dose-response study revealed that 0.4 mL/kg of h-LEH (hemoglobin 24 mg/kg) was effective for elevating bursting pressure at 2 days. h-LEH-treated rats had significantly suppressed HIF-1α accumulation in the wound 6, 24, and 48 h after surgery as compared with control animals treated with homologous RBC or saline. In conclusion, the results suggest that h-LEH, but not l-LEH or homologous transfusion, may accelerate wound healing early after gastric incision and anastomosis in the rat. The mechanism(s) appears to be related to improved O2 supply, aerobic metabolism, and suppressed inflammation in the wound.

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“…It has been our consistent observation that liposome‐encapsulated hemoglobin (LEH), specifically with high O 2 affinity ( h ‐LEH, P 50 O 2 = 8–17 mm Hg), has been associated with suppressed inflammation to promote wound healing , reduce damage after ischemia/reperfusion , and enhance antitumor therapies . Whereas LEH with low O 2 affinity ( l ‐LEH, P 50 O 2 = 40–50 mm Hg) was able to maintain O 2 delivery as a whole in rabbits under hemorrhagic shock, it was not associated with improved peripheral perfusion or extended survival .…”

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confidence: 95%