Oxidative DNA injury after experimental intracerebral hemorrhage

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

doi:10.1016/j.brainres.2005.01.036

Cited by 144 publications

(110 citation statements)

References 34 publications

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“…10 It is well known that brain iron overload can stimulate free radical production and cause oxidative injury, including lipid peroxidation and DNA damage. 18,24,25 The current study shows that injection of lysed RBCs, but not packed RBCs, can mimic the acute ventricular enlargement induced by IVH. …”

Section: Discussionmentioning

confidence: 65%

Role of Red Blood Cell Lysis and Iron in Hydrocephalus after Intraventricular Hemorrhage

Gao

Hua

et al. 2014

J Cereb Blood Flow Metab

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126

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Thrombin and iron are two major players in intracerebral hemorrhage-induced brain injury and our recent study found that thrombin contributes to hydrocephalus development in a rat model of intraventricular hemorrhage (IVH). This study investigated the role of red blood cell (RBC) lysis and iron in hydrocephalus after IVH. There were three parts to this study. First, male SpragueDawley rats received an injection of saline, packed, or lysed RBCs into the right lateral ventricle. Second, rats had an intraventricular injection of iron or saline. Third, the rats received intraventricular injection of lysed RBCs mixed with deferoxamine (0.5 mg in 5 mL saline) or saline. All rats underwent magnetic resonance imaging at 24 hours and were then euthanized for brain edema measurement, western blot analysis, or brain histology. We found that intraventricular injection of lysed RBCs, but not packed RBCs, resulted in ventricular enlargement and marked increases in brain heme oxygenase-1 and ferritin at 24 hours. Intraventricular injection of iron also resulted in ventricular enlargement and ventricular wall damage 24 hours later. Coinjection of deferoxamine reduced lysed RBC-induced ventricular enlargement (Po0.01). These results suggest that iron, a degradation product of hemoglobin, has an important role in hydrocephalus development after IVH.

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Section: Discussionmentioning

confidence: 65%

Role of Red Blood Cell Lysis and Iron in Hydrocephalus after Intraventricular Hemorrhage

Gao

Hua

et al. 2014

J Cereb Blood Flow Metab

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126

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“…The implication of these findings is that increased expression of catalase could contribute to the neuroprotective effect of 15d-PGJ 2 . The inducibility of the catalase gene could play an important role in combating the oxidative stress induced by ICH, as the constitutive level of catalase in the brain is low (Ho et al, 2004) and may not be sufficient to neutralize oxidative stress (Aronowski and Hall, 2005;Nakamura et al, 2005;Wagner et al, 2002). In agreement with this notion, virus-mediated overexpression of the catalase gene in neurons (hippocampal or cortical primary neuronal cultures) increased neuronal resistance to damage produced by excitotoxin or oxygen-glucose deprivation (Wang et al, 2003a).…”

Section: Discussionmentioning

confidence: 92%

15d-Prostaglandin J₂ Activates Peroxisome Proliferator-Activated Receptor-γ, Promotes Expression of Catalase, and Reduces Inflammation, Behavioral Dysfunction, and Neuronal Loss after Intracerebral Hemorrhage in Rats

Zhao¹,

Zhang²,

Strong³

et al. 2006

J Cereb Blood Flow Metab

207

158

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Peroxisome proliferator-activated receptor-c (PPARc) is a transcription factor that regulates the expression of various gene products that are essential in lipid and glucose metabolism, as well as that of the peroxisome-enriched antioxidant enzyme, catalase. Activation of PPARc is linked to antiinflammatory activities and is beneficial for cardiovascular diseases. However, little is known about its role in intracerebral hemorrhage (ICH). 15-Deoxy-D 12,14 -prostaglandin J 2 (15d-PGJ 2 ) acts as a physiologic agonist for PPARc. In this study, we found that injection of 15d-PGJ 2 into the locus of striatal hematoma increased PPARc-deoxyribonucleic acid (DNA) binding activity and the expression of catalase messenger ribonucleic acid (mRNA) and protein in the perihemorrhagic area. Additionally, 15d-PGJ 2 significantly reduced nuclear factor-jB (NF-jB) activation and prevented neutrophil infiltration measured by myeloperoxidase (MPO) immunoassay, and also reduced cell apoptosis measured by terminal deoxynucleotide transferase dUTP nick-end labeling (TUNEL). In addition, 15d-PGJ 2 reduced behavioral dysfunction produced by the ICH. Altogether, our findings indicate that injection of 15d-PGJ 2 at the onset of ICH is associated with activation of PPARc and elevation of catalase expression, suppression of NF-jB activity, and restricted neutrophil infiltration. All these events predicted reduced behavioral deficit and neuronal damage.

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“…Extensive brain edema and brain damage could occur in either the perihematomal or remote brain regions after ICH, thus leading to neurological deficits (Qureshi et al 2001;Wagner et al 2003;Mun-Bryce et al 2004;Hua et al 2006;Xi et al 2006). Toxic hematoma extravasations, such as iron (Wagner et al 2003;Nakamura et al 2005;Hua et al 2006;Okauchi et al 2009), inflammatory cytokines, and thrombin (Mun-Bryce et al 2004;Xi et al 2006;Zhang et al 2006), contribute to the occurrence of neurological deficits. Nevertheless, the mechanism of how toxic hematoma extravasations cause the remote effects of ICH is still unknown.…”

Section: Discussionmentioning

confidence: 99%

Intracerebral Hematoma Extends via Perivascular Spaces and Perineurium

Yin

Lü

Qiu

et al. 2013

Tohoku J. Exp. Med.

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Intracerebral hemorrhage (ICH) is a devastating disorder associated with high morbidity and mortality. ICH results in the formation of hematoma that affects not only the primary site of injury but also the remote regions. In fact, hematoma can extend via perivascular spaces (also called Virchow-Robin spaces, VRS) and perineurium in an animal model of ICH. In the present study, we used magnetic resonance imaging (MRI) with susceptibility-weighted imaging (SWI) to investigate the characteristics of the perivascular and perineural extensions of hematomas in patients with ICH. A total of 20 ICH patients without secondary subarachnoid and secondary intraventricular hemorrhages were recruited. Brain MRI scans, including SWI, T1, and T2-weighted images, were performed between 17 h to 7 days after the onset of ICH. MRI with SWI revealed that paramagnetic substances spread along the VRS or the perineurium. Such distribution could cause the formation of cerebral microbleeds (CMBs). However, the distribution of remote hemorrhagic lesions varied, depending on the size and location of the original hematoma. The unenhanced CT scans of the 20 patients did not show any hyperdensity around the blood vessels and nerve tracts outside the hematoma. These results indicate the perivascular and perineural extensions of hematomas in patients with ICH, which is formed by the leakage of the original hematoma via the VRS or perineurium. We also provide a new explanation for the series of pathological processes involved in ICH, including the remote effects of hematoma and the formation of CMBs in patients with ICH.

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Oxidative DNA injury after experimental intracerebral hemorrhage

Cited by 144 publications

References 34 publications

Role of Red Blood Cell Lysis and Iron in Hydrocephalus after Intraventricular Hemorrhage

Role of Red Blood Cell Lysis and Iron in Hydrocephalus after Intraventricular Hemorrhage

15d-Prostaglandin J₂ Activates Peroxisome Proliferator-Activated Receptor-γ, Promotes Expression of Catalase, and Reduces Inflammation, Behavioral Dysfunction, and Neuronal Loss after Intracerebral Hemorrhage in Rats

Intracerebral Hematoma Extends via Perivascular Spaces and Perineurium

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Oxidative DNA injury after experimental intracerebral hemorrhage

Cited by 144 publications

References 34 publications

Role of Red Blood Cell Lysis and Iron in Hydrocephalus after Intraventricular Hemorrhage

Role of Red Blood Cell Lysis and Iron in Hydrocephalus after Intraventricular Hemorrhage

15d-Prostaglandin J2 Activates Peroxisome Proliferator-Activated Receptor-γ, Promotes Expression of Catalase, and Reduces Inflammation, Behavioral Dysfunction, and Neuronal Loss after Intracerebral Hemorrhage in Rats

Intracerebral Hematoma Extends via Perivascular Spaces and Perineurium

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Product

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15d-Prostaglandin J₂ Activates Peroxisome Proliferator-Activated Receptor-γ, Promotes Expression of Catalase, and Reduces Inflammation, Behavioral Dysfunction, and Neuronal Loss after Intracerebral Hemorrhage in Rats