Iron-induced oxidative brain injury after experimental intracerebral hemorrhage

Nakamura, Takehiro; Keep, Richard F.; Hua, Ya; Nagao, Seigo; Hoff, Julian T.; Xi, Guohua

doi:10.1007/3-211-30714-1_42

Cited by 68 publications

(47 citation statements)

References 12 publications

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“…Clinical evidence has revealed that hematoma volume is one of the major determinants of ICH patient outcomes (37) and iron toxicity from the hematoma exacerbates brain injury (38). Thus, acceleration of hematoma clearance is a logical therapeutic strategy for ICH.…”

Section: Resultsmentioning

confidence: 99%

Erythrocyte efferocytosis modulates macrophages towards recovery after intracerebral hemorrhage

Chang¹,

Goods²,

Askenase³

et al. 2017

Journal of Clinical Investigation

135

161

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-/-bone marrow chimeras (BMCs) at days 7 and 15 after ICH. Right: Quantification of residual hematoma volume in the WT and Ccr2 -/-BMCs. n = 11 at day 7; n = 9 at day 15. *P < 0.05 by Student's t test. (B) Cylinder test and apomorphine turning test from WT and Ccr2 -/-BMCs at day 15 after ICH. n = 6/group for cylinder test; n = 8/ group for apomorphine turning test. *P < 0.05 by Student's t test. (C) Cylinder test, neurological deficit score, and corner test in control-and anti-CCR2 antibody-treated mice at days 1 and 3 after collagenase ICH. n = 7/group. *P < 0.05 by 1-way repeated-measures ANOVA and Bonferroni's post hoc test. (D) Top: Representative coronal sections show hematoma from control-and anti-CCR2 antibody-treated WT mice after blood injection ICH at 7 days. Bottom: Quantification of hematoma volume, n = 3/ group. *P < 0.05 versus control by Student's t test. (E) Top: Representative coronal sections show hematoma in the isotype control-and anti-CCR2 antibody-treated mice from collagenase model at day 12. Bottom: Quantification of hematoma volume. n = 8/group. *P < 0.05 versus control by Student's t test. (F) The cylinder test, neurological deficit score, and corner test in isotype control-and anti-CCR2 antibody-treated ICH mice at days 3, 5, 7, 9, and 11 after collagenase ICH surgery. n = 8/group. *P < 0.05 versus isotype control group by 1-way repeated-measures ANOVA and Bonferroni's post hoc test. αCCR2, anti-CCR2 antibody.

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Section: Resultsmentioning

confidence: 99%

Erythrocyte efferocytosis modulates macrophages towards recovery after intracerebral hemorrhage

Chang¹,

Goods²,

Askenase³

et al. 2017

Journal of Clinical Investigation

135

161

View full text Add to dashboard Cite

show abstract

“…Thrombin is generated quickly in both models and causes rapid BBB disruption and edema when directly injected into the brain. Similarly, iron, which is released from degrading erythrocytes in the days following ICH, causes prominent BBB disruption, edema, and cell death (Huang et al, 2002;Nakamura et al, 2006). The time course of edema is similar in the collagenase and blood infusion models.…”

Section: Outcome End Pointsmentioning

confidence: 99%

A Critical Appraisal of Experimental Intracerebral Hemorrhage Research

MacLellan

Paquette

Colbourne

2012

J Cereb Blood Flow Metab

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The likelihood of translating therapeutic interventions for stroke rests on the quality of preclinical science. Given the limited success of putative treatments for ischemic stroke and the reasons put forth to explain it, we sought to determine whether such problems hamper progress for intracerebral hemorrhage (ICH). Approximately 10% to 20% of strokes result from an ICH, which results in considerable disability and high mortality. Several animal models reproduce ICH and its underlying pathophysiology, and these models have been widely used to evaluate treatments. As yet, however, none has successfully translated. In this review, we focus on rodent models of ICH, highlighting differences among them (e.g., pathophysiology), issues with experimental design and analysis, and choice of end points. A Pub Med search for experimental ICH (years: 2007 to 31 July 2011) found 121 papers. Of these, 84% tested neuroprotectants, 11% tested stem cell therapies, and 5% tested rehabilitation therapies. We reviewed these to examine study quality (e.g., use of blinding procedures) and choice of end points (e.g., behavioral testing). Not surprisingly, the problems that have plagued the ischemia field are also prevalent in ICH literature. Based on these data, several recommendations are put forth to facilitate progress in identifying effective treatments for ICH.

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“…Cell injury results in the release and intracellular accumulation of nonheme iron and the generation of free radicals that react with H 2 O 2 to produce hydroxyl radicals and generate oxidative stress (Davalos et al, 2000;Eaton and Qian, 2002;Hua et al, 2006;Lee et al, 2010;Nakamura et al, 2006;Song et al, 2007). Whereas excess nonheme iron is sequestered by intracellular iron storage and regulatory proteins, such as ferritin, ribonucleotide reductase, transferrin, and ceruloplasmin (Ponka, 2004), excessive accumulation may overwhelm these systems.…”

Section: Figmentioning

confidence: 99%

Prevention of Both Neutrophil and Monocyte Recruitment Promotes Recovery after Spinal Cord Injury

Lee

Rosen

Weinstein

et al. 2011

Journal of Neurotrauma

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Strategies that block infiltration of leukocytes into the injured spinal cord improve sparing of white matter and neurological recovery. In this article, we examine the dependency of recovery on hematogenous depletion of neutrophils and monocytes. Mice were depleted of neutrophils or monocytes by systemic administration of antiLy6G or clodronate-liposomes. A third group was depleted of both subsets. Neurological improvement, based on a battery of tests of performance, and white matter sparing, occurred only in animals depleted of both neutrophils and monocytes. We also attempted to define the nature of the environment that was favorable to recovery. Hemeoxygenase-1 and malondialdehyde, markers of oxidative stress and lipid peroxidation, respectively, were reduced to similar levels in animals depleted of both neutrophils and monocytes, or only monocytes, but remained elevated in the group only depleted of neutrophils. Matrix metalloproteinase-9, a protease involved in early damage, was most strongly reduced in animals depleted of both leukocyte subsets. Finally, disruption of the blood-spinal cord barrier and abnormal nonheme iron accumulation were reduced only in animals depleted of both neutrophils and monocytes. Together, these findings indicate cooperation between neutrophils and monocytes in mediating early pathogenesis in the contused spinal cord and defining long-term neurological recovery.

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Iron-induced oxidative brain injury after experimental intracerebral hemorrhage

Cited by 68 publications

References 12 publications

Erythrocyte efferocytosis modulates macrophages towards recovery after intracerebral hemorrhage

Erythrocyte efferocytosis modulates macrophages towards recovery after intracerebral hemorrhage

A Critical Appraisal of Experimental Intracerebral Hemorrhage Research

Prevention of Both Neutrophil and Monocyte Recruitment Promotes Recovery after Spinal Cord Injury

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