Iron-Induced Necrotic Brain Cell Death in Rats with Different Aerobic Capacity

Zheng, Mingzhe; Du, Hanjian; Ni, Wei; Koch, Lauren G.; Britton, Steven L.; Keep, Richard F.; Xi, Guohua; Hua, Ya

doi:10.1007/s12975-015-0388-8

Cited by 33 publications

(21 citation statements)

References 43 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The slice was separated into the ipsilateral and contralateral basal ganglia. Western blot analysis was performed as previously described [28, 29]. Briefly, 50-μg protein samples were separated by sodium dodecyl sulfate polyacrymide gel electrophoresis and transferred onto a hybond-C pure nitrocellulose membrane (Amersham, Pittsburgh, PA, USA).…”

Section: Methodsmentioning

confidence: 99%

Microglia Activation and Polarization After Intracerebral Hemorrhage in Mice: the Role of Protease-Activated Receptor-1

Wan

Cheng

Jin

et al. 2016

Transl. Stroke Res.

Self Cite

128

103

View full text Add to dashboard Cite

Polarized microglia play a dual (beneficial/detrimental) role in neurological diseases. However, the status and the factors that modulate microglia polarization in intracerebral hemorrhage (ICH) remain unclear. In the present study, we investigated the role of protease-activated receptor-1 (PAR-1, a thrombin receptor) in ICH-induced microglia polarization in mice. Male wild-type (WT) and PAR-1 knockout (PAR-1 KO) mice received an infusion of 30-μL autologous blood or saline into the right basal ganglia. Mice were euthanized at different time points and the brains were used for Western blotting and immunohistochemistry. Some mice had magnetic resonance imaging. We found that ICH induced microglia activation and polarization. M1 phenotypic markers were markedly increased and reached a peak as early as 4 h, remained high at 3 days and decreased 7 days after ICH. M2 phenotypic markers were upregulated later than M1 markers reaching a peak at day 1 and declining by day 7 after ICH. PAR-1 was upregulated after ICH and expressed in the neurons and microglia. ICH induced less brain swelling and neuronal death in PAR-1 KO mice, and this was associated with less M1 polarization and reduced proinflammatory cytokine levels in the brain. In conclusion, these results suggest that polarized microglia occur dynamically after ICH and that PAR-1 plays a role in the microglia activation and polarization.

show abstract

Section: Methodsmentioning

confidence: 99%

Microglia Activation and Polarization After Intracerebral Hemorrhage in Mice: the Role of Protease-Activated Receptor-1

Wan

Cheng

Jin

et al. 2016

Transl. Stroke Res.

Self Cite

128

103

View full text Add to dashboard Cite

show abstract

“…Immunohistochemistry was performed using avidin-biotin complex technique (36, 37). The primary antibodies were rabbit anti-HO-1 (1:400 dilution; Abcam) and rabbit anti-fibrinogen (1:200; Abcam).…”

Section: Methodsmentioning

confidence: 99%

“…Western blot analysis was performed as previously described (23, 36, 38). Briefly, rats were perfused with 0.1mmol/L phosphate buffered saline (pH 7.4) after euthanasia and the ipsi- and contralateral cortex, white matter (corpus callosum) and basal ganglia were sampled.…”

Section: Methodsmentioning

confidence: 99%

MRI Characterization in the Acute Phase of Experimental Subarachnoid Hemorrhage

Guo

Wilkinson

Thompson

et al. 2016

Transl. Stroke Res.

Self Cite

View full text Add to dashboard Cite

A number of mechanisms have been proposed for the early brain injury after subarachnoid hemorrhage (SAH). In this study, we investigated the radiographic characteristics and influence of gender on early brain injury after experimental SAH. SAH was induced by endovascular perforation in male and female rats. Magnetic resonance imaging was performed in a 7.0-T Varian MR scanner at 24 hours after SAH. The occurrence and size of T2 lesions, ventricular dilation and white matter injury (WMI) was determined on T2 weighted images (T2WI). The effects of SAH on heme oxygenase-1 and fibrin/fibrinogen were examined by Western blotting and immunohistochemistry. SAH severity was assessed using a MRI grading system and neurological function was evaluated according to a modified Garcia’s scoring system. T2-hyperintensity areas and enlarged ventricles were observed in T2WI coronal sections 24 hours after SAH. The overall incidence of T2-lesions, WMI and hydrocephalus was 54, 20 and 63%, respectively. Female rats had a higher incidence of T2-hyperintensity lesions and hydrocephalus, as well as larger T2 lesion volumes and higher average ventricular volume. SAH rats graded at 3-4 (our previously validated MRI grading scale) had larger T2 lesion volumes, more hydrocephalus and worse neurological function compared with those graded at 0-2. In conclusion, T2-lesion, WMI and hydrocephalus were the most prevalent MRI characteristics 24 hours after experimental SAH. The T2-lesion area matched with fibrinogen/fibrin positive staining in the acute phase of SAH. SAH induced more severe brain injury in females compared to males in the acute phase of SAH.

show abstract

“…This may lead to direct inflammation and choroidal and retinal injury with time. We propose iron-accumulation within these cellular structures is associated with promotion of oxidative stress, 28 inflammation and membrane attack complex formation, as suggested by brain studies, 29 may contribute to reduced choroidal function with aging. Membrane attack complex formation, the terminal process of complement activation, which can cause cell death, has been shown to increase in the inner choroid during normal aging and especially in age-related macular degeneration.…”

Section: Metallomics Papermentioning

confidence: 68%

Iron accumulates in the primate choroid of the eye with aging as revealed with synchrotron X-ray fluorescence microscopy

Ugarte

Geraki

Jeffery³

2016

Metallomics

View full text Add to dashboard Cite

Aging leads to an increase in iron-loaded cellular structures in the choroid of the eye. This study was carried out to determine the distribution and content of iron, zinc and copper in the macular retina, choroid and retrobulbar optic nerve of young (4-5 years, n = 3) and aged (15-16 years, n = 5) male non-human primates, Macaca fascicularis, whose ocular anatomy is similar to humans. Thirty μm-thick tissue sections were analysed with synchrotron X-ray fluorescence and stained histologically for iron deposition. Quantitative measurements showed high levels of iron, zinc and copper in the choroid and retinal pigment epithelium in the macular area and arachnoid layer in the retrobulbar optic nerve. In aged animals compared to young ones, there was an increase in iron in the choroid with larger deposits and iron-loaded cellular structures. Iron-accumulation within these cellular structures may contribute to choroidal function impairment in aging and age-related macular degeneration.

show abstract

Iron-Induced Necrotic Brain Cell Death in Rats with Different Aerobic Capacity

Cited by 33 publications

References 43 publications

Microglia Activation and Polarization After Intracerebral Hemorrhage in Mice: the Role of Protease-Activated Receptor-1

Microglia Activation and Polarization After Intracerebral Hemorrhage in Mice: the Role of Protease-Activated Receptor-1

MRI Characterization in the Acute Phase of Experimental Subarachnoid Hemorrhage

Iron accumulates in the primate choroid of the eye with aging as revealed with synchrotron X-ray fluorescence microscopy

Contact Info

Product

Resources

About