Hydrocephalus after Intraventricular Hemorrhage: The Role of Thrombin

Gao, Feng; Liu, Fuyi; Chen, Zhi; Hua, Ya; Keep, Richard F.; Xi, Guohua

doi:10.1038/jcbfm.2013.225

Cited by 82 publications

(89 citation statements)

References 29 publications

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“…p-mTOR mediated) that are potentially upstream of ECM protein dysregulation. 1, 5, 7–9, 11, 14 Multiple parallels (especially thrombin) 1, 2, 7–11 exist between our study, and the pathophysiology of adult intracerebral hemorrhage. 4, 5, 12–14 Thus in extension: our findings may have a much broader therapeutic implication in terms of further adult stroke mechanistic study (for detailed comparisons, however—please reference 15 , these fall outside the scope of this paper).…”

Section: Discussionsupporting

confidence: 51%

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Protease-Activated Receptor 1 and 4 Signal Inhibition Reduces Preterm Neonatal Hemorrhagic Brain Injury

Lekic

Klebe

McBride

et al. 2015

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Background and Purpose— This study examines the role of thrombin’s protease-activated receptor (PAR)-1, PAR-4 in mediating cyclooxygenase-2 and mammalian target of rapamycin after germinal matrix hemorrhage. Methods— Germinal matrix hemorrhage was induced by intraparenchymal infusion of bacterial collagenase into the right ganglionic eminence of P7 rat pups. Animals were treated with PAR-1, PAR-4, cyclooxygenase-2, or mammalian target of rapamycin inhibitors by 1 hour, and ≤5 days. Results— We found increased thrombin activity 6 to 24 hours after germinal matrix hemorrhage, and PAR-1, PAR-4, inhibition normalized cyclooxygenase-2, and mammalian target of rapamycin by 72 hours. Early treatment with NS398 or rapamycin substantially improved long-term outcomes in juvenile animals. Conclusions— Suppressing early PAR signal transduction, and postnatal NS398 or rapamycin treatment, may help reduce germinal matrix hemorrhage severity in susceptible preterm infants.

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Section: Discussionsupporting

confidence: 51%

“…5 Thrombin activates a subfamily of G protein-coupled receptors, named proteinase-activated-receptors (PAR; specifically -1 and -4), 6 leading to phosphorylation and activation of mTOR 7 and increased COX-2 expression. 8 …”

Section: Introductionmentioning

confidence: 99%

Protease-Activated Receptor 1 and 4 Signal Inhibition Reduces Preterm Neonatal Hemorrhagic Brain Injury

Lekic

Klebe

McBride

et al. 2015

Stroke

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“…Our recent study showed that thrombin contributes to IVH-induced hydrocephalus. 4 There have been few studies evaluating the relationship between iron released from blood into cerebrospinal fluid (CSF) and hydrocephalus; however, there is some clinical evidence of a link between iron and posthemorrhagic hydrocephalus. Nonprotein-bound iron was found in CSF from preterm infants with posthemorrhagic ventricular dilatation compared with infants without IVH.…”

Section: Introductionmentioning

confidence: 99%

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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118

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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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“…Increased brain HO-1 levels may accelerate heme degradation and result in brain damage after ICH and SAH 23, 38, 39 . However, some literature report a protective function 40 and, in the current study, CD47 KO blood increased HO-1 levels and was associated with reduced ICH-induced brain injury.…”

Section: Discussionmentioning

confidence: 99%

Role of Erythrocyte CD47 in Intracerebral Hematoma Clearance

Mao

et al. 2016

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Background and Purpose Enhancing hematoma clearance through phagocytosis may reduce brain injury after intracerebral hemorrhage (ICH). In the current study, we investigated the role of CD47 in regulating erythrophagocytosis and brain injury after ICH in nude mice. Methods This study was in two parts. First, male adult nude mice had an intracaudate injection of 30-µl saline, blood from male adult wild type (WT) mice or blood from CD47 knockout (CD47 KO) mice. Second, mice had an intracaudate injection of 30-µl CD47 KO blood with clodronate or control liposomes. Clodronate liposomes were also tested in saline-injected mice. All mice then had magnetic resonance imaging to measure hematoma size and brain swelling. Brains were used for immunohistochemistry and Western blot. Results Erythrophagocytosis occurred in and around the hematoma. Injection of CD47 KO blood resulted in quicker clot resolution, less brain swelling, and less neurological deficits compared to WT blood. Higher brain heme oxygenase-1 levels and more microglial activation (mostly M2 polarized microglia) at day-3 were found after CD47 KO blood injection. Co-injection of clodronate liposomes, to deplete phagocytes, caused more severe brain swelling and less clot resolution. Conclusion These results indicated CD47 has a key role in hematoma clearance after ICH.

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Hydrocephalus after Intraventricular Hemorrhage: The Role of Thrombin

Cited by 82 publications

References 29 publications

Protease-Activated Receptor 1 and 4 Signal Inhibition Reduces Preterm Neonatal Hemorrhagic Brain Injury

Protease-Activated Receptor 1 and 4 Signal Inhibition Reduces Preterm Neonatal Hemorrhagic Brain Injury

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

Role of Erythrocyte CD47 in Intracerebral Hematoma Clearance

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