Deferoxamine reduces intracerebral hemorrhage-induced white matter damage in aged rats

Ni, Wei; Okauchi, Masanobu; Hatakeyama, Tetsuhiro; Gu, Yuxiang; Keep, Richard F.; Xi, Guohua; Hua, Ya

doi:10.1016/j.expneurol.2015.02.035

Cited by 37 publications

(39 citation statements)

References 29 publications

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“…The efficacy of free radical scavengers has provided direct evidence for a causal relationship between ROS and ICH injury. Specifically, overexpression of copper/zinc-superoxide dismutase (Wakai, et al, 2014) or treatment with deferoxamine (Cui, et al, 2015, Ni, et al, 2015, H. Wu, et al, 2011), a chelator of pro-oxidative iron, significantly reduced brain injury in animal models of ICH.…”

Section: Discussionmentioning

confidence: 99%

Progesterone exerts neuroprotective effects and improves long-term neurologic outcome after intracerebral hemorrhage in middle-aged mice

Jiang

Zuo

Wang

et al. 2016

Neurobiology of Aging

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In this study, we examined the effect of progesterone on histopathologic and functional outcomes of intracerebral hemorrhage (ICH) in 10–12-month-old mice. Progesterone or vehicle was administered by intraperitoneal injection 1 hour after collagenase-induced ICH and then by subcutaneous injections at 6, 24, and 48 hours. Oxidative and nitrosative stress were assayed at 12 hours post-ICH. Injury markers were examined on day 1, and lesion was examined on day 3. Neurologic deficits were examined for 28 days. Progesterone posttreatment reduced lesion volume, brain swelling, edema, and cell degeneration and improved long-term neurologic function. These protective effects were associated with reductions in protein carbonyl formation, protein nitrosylation, and MMP-9 activity and attenuated cellular and molecular inflammatory responses. Progesterone also reduced VEGF expression, increased neuronal-specific Na+/K+ ATPase α3 subunit expression, and reduced PKC-dependent Na+/K+ ATPase phosphorylation. Furthermore, progesterone reduced glial scar thickness, myelin loss, brain atrophy, and residual injury volume on day 28 after ICH. With multiple brain targets, progesterone warrants further investigation for its potential use in ICH therapy.

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Section: Discussionmentioning

confidence: 99%

Progesterone exerts neuroprotective effects and improves long-term neurologic outcome after intracerebral hemorrhage in middle-aged mice

Jiang

Zuo

Wang

et al. 2016

Neurobiology of Aging

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“…DFX has recently been reported to downregulate expression of p-JNK in the basal ganglia linking JNK to Fe (Ni et al, 2015). JNK is a member of the MAPK signaling pathway that is activated by cytokines and environmental stress (Weston and Davis, 2007).…”

Section: Discussionmentioning

confidence: 99%

Hemoglobin-induced neuronal degeneration in the hippocampus after neonatal intraventricular hemorrhage

Garton

et al. 2016

Brain Research

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Neuronal degeneration following neonatal intraventricular hemorrhage (IVH) is incompletely understood. Understanding the mechanisms of degeneration and cell loss may point toward specific treatments to limit injury. We evaluated the role of hemoglobin (Hb) in cell death after intraventricular injection in neonatal rats. Hb was injected into the right lateral ventricle of post-natal day 7 rats. Rats exposed to anesthesia were used for controls. The CA-1 region of the hippocampus was analyzed via immunohistochemistry, hematoxylin and eosin (H&E) staining, Fluoro-Jade C staining, Western blots, and double-labeling stains. Compared to controls, intraventricular injection of Hb decreased hippocampal volume (27% decrease; p<0.05), induced neuronal loss (31% loss; p<0.01), and increased neuronal degeneration (2.7 fold increase; p<0.01), which were all significantly reduced with the iron chelator, deferoxamine. Hb upregulated p-JNK (1.8 fold increase; p<0.05) and increased expression of the Hb/haptoglobin endocytotic receptor CD163 in neurons in vivo and in vitro (cultured cortical neurons). Hb induced expression of the CD163 receptor, which co-localized with p-JNK in hippocampal neurons, suggesting a potential pathway by which Hb enters the neuron to result in cell death. There were no differences in neuronal loss or degenerating neurons in Hb-injected animals that developed hydrocephalus versus those that did not. Intraventricular injection of Hb causes hippocampal neuronal degeneration and cell loss and increases brain p-JNK levels. p-JNK co-localized with the Hb/haptoglobin receptor CD163, suggesting a novel pathway by which Hb enters the neuron after IVH to result in cell death.

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“…Our previous studies have demonstrated that ICH activated the JNK signaling pathway in WM bundles in rats. Deferoxamine, an iron chelator, reduced ICH‐induced JNK activation and white matter loss . Other reports demonstrated that suppressing P38 MAPK activation confers neuroprotection in rat intracerebral hemorrhage .…”

Section: Discussionmentioning

confidence: 94%

“…[4][5][6] Our previous work has shown that ICH-induced iron toxicity causes WM injury through c-Jun N-terminal kinase (JNK) and receptor-interacting protein kinase 1 (RIPK1) activation. 7 Because of white matter's critical role in neurotransmission, WM injury may also lead to severe sensorimotor dysfunction, neurobehavioral impairment, and cognitive disorders. 8,9 Therefore, protecting against WM injury after ICH is a pressing concern.…”

Section: Backg Rou N Dmentioning

confidence: 99%

Minocycline reduces intracerebral hemorrhage–induced white matter injury in piglets

Yang

Gao

et al. 2019

CNS Neurosci Ther

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Aims White matter (WM) injury after intracerebral hemorrhage (ICH) results in poor or even fatal outcomes. As an anti‐inflammatory drug, minocycline has been considered a promising choice to treat brain injury after ICH. However, whether minocycline can reduce WM injury after ICH is still controversial. In the present study, we investigate the effect and underlying mechanism of minocycline on WM injury after ICH. Methods An ICH model was induced by an injection of autologous blood into the right frontal lobe of piglets. First, transcriptional analysis was performed at day 1 or 3 to investigate the dynamic changes in neuroinflammatory gene expression in WM after ICH. Second, ICH piglets were treated either with minocycline or with vehicle alone. All piglets then underwent magnetic resonance imaging to measure brain swelling. Brain tissue was used for real‐time polymerase chain reaction (RT‐PCR), immunohistochemistry, Western blot, and electron microscopy. Results Transcriptional analysis demonstrated that transforming growth factor‐β (TGF‐β)/mitogen‐activated protein kinase (MAPK) signaling is associated with microglia/macrophage‐mediated inflammation activation after ICH and is then involved in WM injury after ICH in piglets. Minocycline treatment results in less ICH‐induced brain swelling, fewer neurological deficits, and less WM injury in comparison with the vehicle alone. In addition, minocycline reduces microglial activation and alleviates demyelination in white matter after ICH. Finally, we found that minocycline attenuates WM injury by increasing the expression of TGF‐β and suppressing MAPK activation after ICH. Conclusion These results indicate that TGF‐β–mediated MAPK signaling contributes to WM injury after ICH, which can be altered by minocycline treatment.

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Deferoxamine reduces intracerebral hemorrhage-induced white matter damage in aged rats

Cited by 37 publications

References 29 publications

Progesterone exerts neuroprotective effects and improves long-term neurologic outcome after intracerebral hemorrhage in middle-aged mice

Progesterone exerts neuroprotective effects and improves long-term neurologic outcome after intracerebral hemorrhage in middle-aged mice

Hemoglobin-induced neuronal degeneration in the hippocampus after neonatal intraventricular hemorrhage

Minocycline reduces intracerebral hemorrhage–induced white matter injury in piglets

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