Experimental Intracerebral Hemorrhage in Rats

Mr, Del Bigio; Huang, Yan; Buist, Richard; Peeling, James

doi:10.1161/01.str.27.12.2312

Cited by 214 publications

(119 citation statements)

References 37 publications

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“…The neutrophils themselves are expected to die by apoptosis within 2 days of entering the hematoma (Savill and Haslett, 2001). An influx of neutrophils was found in a collagenase-or collagenase/heparininduced model of ICH in rat (Del Bigio et al, 1996;Mayne et al, 2001a;Peeling et al, 2001b). Moreover, neutrophil infiltration has been shown to have similar temporal patterns in both rat ICH models Xue and Del Bigio, 2000a).…”

Section: Leukocytesmentioning

confidence: 86%

“…Animal models of ICH provide substantial evidence for the presence of white blood cell infiltration into the hematoma (Del Bigio et al, 1996;Gong et al, 2000;Mayne et al, 2001a;Peeling et al, 2001b;Wang and Tsirka, 2005b;Xue and Del Bigio, 2000a, b;Zhao et al, 2006b). In a rat autologous blood model, neutrophil infiltration was found in and around the hematoma, which begins in less than 1 day, peaks at 2 to 3 days, and almost disappears at 3 to 7 days (Gong et al, 2000;Xue and Del Bigio, 2000a, b).…”

Section: Leukocytesmentioning

confidence: 99%

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Inflammation after Intracerebral Hemorrhage

Wang

Doré

2007

J Cereb Blood Flow Metab

583

609

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Intracerebral hemorrhage (ICH) is a devastating clinical event without effective therapies. Increasing evidence suggests that inflammatory mechanisms are involved in the progression of ICH-induced brain injury. Inflammation is mediated by cellular components, such as leukocytes and microglia, and molecular components, including prostaglandins, chemokines, cytokines, extracellular proteases, and reactive oxygen species. Better understanding of the role of the ICH-induced inflammatory response and its potential for modulation might have profound implications for patient treatment. In this review, a summary of the available literature on the inflammatory responses after ICH is presented along with discussion of some of the emerging opportunities for potential therapeutic strategies. In the near future, additional strategies that target inflammation could offer exciting new promise in the therapeutic approach to ICH.

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Section: Leukocytesmentioning

confidence: 86%

Section: Leukocytesmentioning

confidence: 99%

Inflammation after Intracerebral Hemorrhage

Wang

Doré

2007

J Cereb Blood Flow Metab

583

609

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“…Administration of TS-011 at a dose of 0.1 mg/kg significant reduced infarct size and the degree of neurological deficit in rats following this model of ICH. The neurological deficits in this model is thought to be due the destruction of brain tissue secondary to cerebral edema and reduced blood flow in the affected tissue (Jenkins et al, 1989;Del Bigio et al, 1996). Although the mechanism of the beneficial effect of TS-011 remains to be determined, one likely possibility is that TS-011 might improve the rCBF following ICH by preventing acute vasospasm similar to its effects following SAH.…”

Section: Discussionmentioning

confidence: 98%

“…We also examined the effects of TS-011 on infarct size in a collagenase-induced model of intracerebral hemorrhage (Del Bigio et al, 1996). Briefly, 8-week-old Sprague-Dawley rats purchased from Charles River Laboratories, Inc. were anesthetized with thiopental (30 mg/kg i.p.…”

Section: Effects Of Pretreatment Of Rats With Ts-011 On the Acute Falmentioning

confidence: 99%

Beneficial Effects of a New 20-Hydroxyeicosatetraenoic Acid Synthesis Inhibitor, TS-011 [N-(3-Chloro-4-morpholin-4-yl) Phenyl-N′-hydroxyimido Formamide], on Hemorrhagic and Ischemic Stroke

Miyata

Seki²,

Tanaka³

et al. 2005

J Pharmacol Exp Ther

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The present study characterized the effects of TS-011 [N-(3-chloro-4-morpholin-4-yl) phenyl-NЈ-hydroxyimido formamide], a new selective inhibitor of the synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE), on the metabolism of arachidonic acid by human and rat renal microsomes and the inhibitory effects of this compound on hepatic cytochrome P450 enzymes involved in drug metabolism. The effects of TS-011 on the fall in cerebral blood flow following subarachnoid hemorrhage (SAH) and in reducing infarct size in ischemic stroke models were also examined since 20-HETE may contribute to the development of cerebral vasospasm. TS-011 inhibited the synthesis of 20-HETE by human renal microsomes and recombinant CYP4A11 and 4F2, 4F3A, and 4F3B enzymes with IC 50 values around 10 to 50 nM. It had no effect on the activities of CYP1A, 2C9, 2C19, 2D6, or 3A4 enzymes. TS-011 inhibited the synthesis of 20-HETE by rat renal microsomes with an IC 50 of 9.19 nM, and it had no effect on epoxygenase activity at a concentration of 100 M. TS-011 (0.01-1 mg/kg i.v.) reversed the fall in cerebral blood flow and the increase in 20-HETE levels in the cerebrospinal fluid of rats after SAH. TS-011 also reduced the infarct volume by 35% following transient ischemic stroke and in intracerebral hemorrhage in rats. Injection of 20-HETE (8 or 12 mg/kg) into the carotid artery produced an infarct similar to that seen in the ischemic stroke model. These studies indicate that blockade of the synthesis of 20-HETE with TS-011 opposes cerebral vasospasm following SAH and reduces infarct size in ischemic models of stroke.Each year, 750,000 strokes occur in the United States. Approximately 80% of the strokes are ischemic, and 20% are hemorrhagic. Hemorrhagic stroke commonly occurs after rupture of aneurysms or head trauma. There is an initial period of cerebral ischemia lasting several hours due to a rise in cerebral spinal fluid (CSF) pressure and acute cerebral vasospasm. One-half of the patients that survive later develop delayed vasospasm. The mortality in the 1st month hovers around 50%. The majority of deaths (Ͼ60%) occur during the first 2 days and is associated with ischemic brain injury (Broderick et al., 1994). The factors that contribute to the acute fall in cerebral blood flow following subarachnoid hemorrhage (SAH) remain uncertain.Ischemic strokes are caused by blockage of cerebral arteries. In the ischemic neuronal tissue, there is depletion of

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“…It was initially thought that collagenase injection into the brain parenchyma might be directly toxic or result in an exaggerated immune and thus inflammatory response different from the mechanism producing human ICH (Del Bigio et al, 1996;Xue and Del Bigio, 2003). However, in vitro studies of inflammation and apoptosis simultaneously utilizing both autologous blood and collagenase models argue against this (Chu et al, 2004;Matsushita et al, 2000).…”

Section: Minimizing Excess Inflammationmentioning

confidence: 99%

Experimental Intracerebral Hemorrhage: Avoiding Pitfalls in Translational Research

Kirkman

Allan

Parry‐Jones

2011

J Cereb Blood Flow Metab

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Intracerebral hemorrhage (ICH) has the highest mortality of all stroke subtypes, yet treatments are mainly limited to supportive management, and surgery remains controversial. Despite significant advances in our understanding of ICH pathophysiology, we still lack preclinical models that accurately replicate the underlying mechanisms of injury. Current experimental ICH models (including autologous blood and collagenase injection) simulate different aspects of ICH-mediated injury but lack some features of the clinical condition. Newly developed models, notably hypertension-and oral anticoagulant therapy-associated ICH models, offer added benefits but further study is needed to fully validate them. Here, we describe and discuss current approaches to experimental ICH, with suggestions for changes in how this condition is studied in the laboratory. Although advances in imaging over the past few decades have allowed greater insight into clinical ICH, there remains an important role for experimental models in furthering our understanding of the basic pathophysiologic processes underlying ICH, provided limitations of animal models are borne in mind. Owing to differences in existing models and the failed translation of benefits in experimental ICH to clinical practice, putative neuroprotectants should be trialed in multiple models using both histological and functional outcomes until a more accurate model of ICH is developed.

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Experimental Intracerebral Hemorrhage in Rats

Cited by 214 publications

References 37 publications

Inflammation after Intracerebral Hemorrhage

Inflammation after Intracerebral Hemorrhage

Beneficial Effects of a New 20-Hydroxyeicosatetraenoic Acid Synthesis Inhibitor, TS-011 [N-(3-Chloro-4-morpholin-4-yl) Phenyl-N′-hydroxyimido Formamide], on Hemorrhagic and Ischemic Stroke

Experimental Intracerebral Hemorrhage: Avoiding Pitfalls in Translational Research

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