Deferoxamine Reduces Neuronal Death and Hematoma Lysis After Intracerebral Hemorrhage in Aged Rats

Hatakeyama, Tetsuhiro; Okauchi, Masanobu; Hua, Ya; Keep, Richard F.; Xi, Guohua

doi:10.1007/s12975-013-0270-5

Cited by 84 publications

(63 citation statements)

References 41 publications

(46 reference statements)

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“…Iron overload caused by ICH is an important contributor to neurobiological deficits, brain edema, inflammation, neuron apoptosis and brain atrophy. These effects can be reduced with deferoxamine, an iron chelator [38][39][40][41][42][43][44][45] . However, two studies [46,47] have reported that deferoxamine reduces the level of iron, but does not improve outcomes, in a collagenase-induced ICH model.…”

Section: Discussionmentioning

confidence: 99%

Curcumin attenuates brain edema in mice with intracerebral hemorrhage through inhibition of AQP4 and AQP9 expression

et al. 2015

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Aim: Aquaporins (AQPs) are the water-channels that play important roles in brain water homeostasis and in cerebral edema induced by brain injury. In this study we investigated the relationship between AQPs and a neuroprotective agent curcumin that was effective in the treatment of brain edema in mice with intracerebral hemorrhage (ICH). Methods: ICH was induced in mice by autologous blood infusion. The mice immediately received curcumin (75, 150, and 300 mg/kg, ip). The Rotarod test scores, brain water content and brain expression of AQPs were measured post ICH. Cultured primary mouse astrocytes were used for in vitro experiments. The expression of AQP1, AQP4 and AQP9 and NF-κB p65 were detected using Western blotting or immunochemistry staining. Results: Curcumin administration dose-dependently reduced the cerebral edema at d 3 post ICH, and significantly attenuated the neurological deficits at d 5 post ICH. Furthermore, curcumin dose-dependently decreased the gene and protein expression of AQP4 and AQP9, but not AQP1 post ICH. Treatment of the cultured astrocytes with Fe 2+ (10-100 µmol/L) dose-dependently increased the expression and nuclear translocation of NF-κB p65 and the expression of AQP4 and AQP9, which were partly blocked by co-treatment with curcumin (20 µmol/L) or the NF-κB inhibitor PDTC (10 µmol/L). Conclusion: Curcumin effectively attenuates brain edema in mice with ICH through inhibition of the NF-κB pathway and subsequently the expression of AQP4 and AQP9. Curcumin may serve as a potential therapeutic agent for ICH.

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Section: Discussionmentioning

confidence: 99%

Curcumin attenuates brain edema in mice with intracerebral hemorrhage through inhibition of AQP4 and AQP9 expression

et al. 2015

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“…DFX can reduce free iron in cerebrospinal fluid as well as ICH-induced neurological deficits and acute neuronal death in rat experiment. It can also inhibit the endogenous response to ICH and the upregulation of ferritin and AQP4, which are related to a poor outcome of ICH [46,89,90] . Pro-oxidant heme, which is released from Hb catabolism of heme, plays an important role in the resolution of hematoma.…”

Section: Inhibition Of Rbcs Lysis and Hb Toxicitymentioning

confidence: 99%

Mechanism and Therapy of Brain Edema after Intracerebral Hemorrhage

et al. 2016

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Background: Intracerebral hemorrhage (ICH) is a subtype of stroke with a severe high mortality and disability rate and accounts for about 10-15% of all strokes. The oppression and destruction by hematoma to brain tissue cause the primary brain injury. The inflammation and coagulation response after ICH would accelerate the formation of brain edema around hematoma, resulting in a more severe and durable injury. Currently, treatments for ICH are focusing on the primary injury including reducing intracranial hypertension, blood pressure control, and rehabilitation. There is a short-of-effective medical treatment for secondary inflammation and reducing brain edema in ICH patients. So, it is very important to study on the relationship between brain edema and ICH. Summary: Many molecular and cellular mechanisms contribute to the formation and progress of brain edema after ICH; inhibition of brain edema provides favorable outcome of ICH. Key Messages: This review mainly discusses the pathology and mechanism of brain edema, the effects of brain edema on ICH, and the methods of treating brain edema after ICH.

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“…Blood lysis starts at 24 h and continues for the next several days, leading to the release of cytotoxic hemoglobin (Hb) with further deterioration of the pathological status quo [2]. Iron, a major hemoglobin degradation product which accumulates in the brain parenchyma for months, has a detrimental effect in secondary injury [3][4][5][6][7]. Iron plays a key role in edema formation and cell death after ICH [5,8].…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, exogenous iron chelation therapy seems to be a logical approach to remove toxic levels of iron. Deferoxamine, a ferric iron chelator, which is the most popular treatment in experimental intervention strategy in ICH, has been shown to mitigate iron-mediated damage [3,4]. Unfortunately, recent data showed that deferoxamine can reduce the iron contents in the brain, but could not attenuate injury and improve neurological outcome [10,11].…”

Section: Introductionmentioning

confidence: 99%

Effect Comparison of Both Iron Chelators on Outcomes, Iron Deposit, and Iron Transporters After Intracerebral Hemorrhage in Rats

Wang

Tang

et al. 2015

Mol Neurobiol

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Iron overload plays a key role in brain injury after intracerebral hemorrhage (ICH). We explored the roles of ferric iron chelator-deferiprone (DFP)-and ferrous iron chelator-clioquinol (CQ)-in ICH rats through the outcomes, iron deposits, reactive oxygen species (ROS), brain water content, and related iron transporters. One hundred eight Sprague-Dawley rats received intra-striatal infusions of 0.5 U of type IV collagenase to establish ICH models. The rats were randomly assigned to the sham, vehicle, DFP, and CQ groups. We evaluated the outcomes, iron levels, brain water content, and ROS; meanwhile, immunohistochemistry and real-time quantitative polymerase chain reaction (RT-qPCR) were utilized to determine ferritin, transferrin, transferrin receptor, divalent metal transport 1 (DMT1), and ferroportin at 48 and 72 h, 7 and 14 days after surgery. Our results showed ICH induced iron overload, brain edema, ROS formation, and neurological deficits. Both iron chelators decreased iron levels; CQ improved the neurological outcome, attenuated brain edema, and ROS production. DFP reduced iron contents but not brain water content and ROS generation. DFP failed to improve the outcome. ICH initiated endogenous iron chelators and transporters, both exogenous iron chelators enhanced expression of transferrin and transferrin receptor. CQ enhanced expression of ferroportin but not DMT1, while DFP enhanced expression of DMT1 but not ferroportin. Ferrous iron contributed to brain injury, and binding ferrous iron can modestly improve outcome after ICH in rats. The exogenous ferrous iron chelator possibly functioned via endogenous ferrous iron transporters on ICH. Therefore, ferrous iron may be a promising target for ICH in future.

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Deferoxamine Reduces Neuronal Death and Hematoma Lysis After Intracerebral Hemorrhage in Aged Rats

Cited by 84 publications

References 41 publications

Curcumin attenuates brain edema in mice with intracerebral hemorrhage through inhibition of AQP4 and AQP9 expression

Curcumin attenuates brain edema in mice with intracerebral hemorrhage through inhibition of AQP4 and AQP9 expression

Mechanism and Therapy of Brain Edema after Intracerebral Hemorrhage

Effect Comparison of Both Iron Chelators on Outcomes, Iron Deposit, and Iron Transporters After Intracerebral Hemorrhage in Rats

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