Brain edema after intracerebral hemorrhage in rats: the role of iron overload and aquaporin 4

Qing, Wang Gai; Dong, Yang; Ping, Tang; Lai, Li Guang; Fang, Li Dong; Min, Hu; Lian, Xin; Heng, Pei Yu

doi:10.3171/2008.4.jns17512

Cited by 92 publications

(75 citation statements)

References 36 publications

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“…In rodent whole-blood and collagenase ICH models, deferoxamine has been shown to decrease edema and oxidative DNA damage, while preventing brain atrophy and improving neurological function. 50,58,88 Furthermore, these results have been corroborated in aged rats and piglets. 22,23,26,54,55 It should be noted, however, that 2 studies of deferoxamine in rat collagenase models found no improvement in neurobehavioral function.…”

Section: Therapies Under Investigationsupporting

confidence: 66%

Emerging experimental therapies for intracerebral hemorrhage: targeting mechanisms of secondary brain injury

Belur

Chang²,

He³

et al. 2013

FOC

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Intracerebral hemorrhage (ICH) is associated with a higher degree of morbidity and mortality than other stroke subtypes. Despite this burden, currently approved treatments have demonstrated limited efficacy. To date, therapeutic strategies have principally targeted hematoma expansion and resultant mass effect. However, secondary mechanisms of brain injury are believed to be critical effectors of cell death and neurological outcome following ICH. This article reviews the pathophysiology of secondary brain injury relevant to ICH, examines pertinent experimental models, and highlights emerging therapeutic strategies. Treatment paradigms discussed include thrombin inhibitors, deferoxamine, minocycline, statins, granulocyte-colony stimulating factors, and therapeutic hypothermia. Despite promising experimental and preliminary human data, further studies are warranted prior to effective clinical translation.

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Section: Therapies Under Investigationsupporting

confidence: 66%

Emerging experimental therapies for intracerebral hemorrhage: targeting mechanisms of secondary brain injury

Belur

Chang²,

He³

et al. 2013

FOC

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“…These novel findings suggest that curcumin could be used as an AQP4 and AQP9 inhibitor in the clinical treatment of ICH patients. Iron, a byproduct of hemoglobin degradation, has been shown to play a major role in ICH-induced brain edema and brain damage [34][35][36][37] . Iron overload caused by ICH is an important contributor to neurobiological deficits, brain edema, inflammation, neuron apoptosis and brain atrophy.…”

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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“…Subacute (within 2 days of ICH) activation of the coagulation cascade and release of thrombin contributes to cerebral edema development. This is further worsened by the erythrocyte lysis and hemoglobin (Hb) toxicity taking place primarily during the later stages [28]. The BBB disruption, induced by thrombin, MMPs, complement proteins and hemolytic byproducts, manifests 8–12 h after ICH onset and is also implicated in cerebral edema formation [9,8,29].…”

Section: Mechanisms Of Ich-induced Secondary Brain Injurymentioning

confidence: 99%

“…2). Deferoxamine may also attenuate cytotoxic edema formation through modulation of aquaporin-4 channel expression [28]. Systemic administration of deferoxamine in ICH models reduced the severity of oxidative damage and cerebral edema, and also led to improved neurological and functional outcome [55,56].…”

Section: Therapeutic Targets and Strategiesmentioning

confidence: 99%

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Advances in Neuroprotective Strategies: Potential Therapies for Intracerebral Hemorrhage

et al. 2010

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Intracerebral hemorrhage (ICH) is associated with higher mortality and morbidity than any other form of stroke. However, there currently are no treatments proven to improve outcomes after ICH, and therefore, new effective therapies are urgently needed. Growing insight into ICH pathophysiology has led to the development of neuroprotective strategies that aim to improve the outcome through reduction of secondary pathologic processes. Many neuroprotectants target molecules or pathways involved in hematoma degradation, inflammation or apoptosis, and have demonstrated potential clinical benefits in experimental settings. We extensively reviewed the current understanding of ICH pathophysiology as well as promising experimental neuroprotective agents with particular focus on their mechanisms of action. Continued advances in ICH knowledge, increased understanding of neuroprotective mechanisms, and improvement in the ability to modulate molecular and pathologic events with multitargeting agents will lead to successful clinical trials and bench-to-bedside translation of neuroprotective strategies.

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Brain edema after intracerebral hemorrhage in rats: the role of iron overload and aquaporin 4

Cited by 92 publications

References 36 publications

Emerging experimental therapies for intracerebral hemorrhage: targeting mechanisms of secondary brain injury

Emerging experimental therapies for intracerebral hemorrhage: targeting mechanisms of secondary brain injury

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

Advances in Neuroprotective Strategies: Potential Therapies for Intracerebral Hemorrhage

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