Systemic Administration of Argatroban Reduces Secondary Brain Damage in a Rat Model of Intracerebral Hemorrhage: Histopathological Assessment

Nagatsuna, Toshikazu; Nomura, Sadahiro; Suehiro, Eiichi; Fujisawa, Hironori; Koizumi, Hiroyasu; Suzuki, Michiyasu

doi:10.1159/000083466

Cited by 35 publications

(26 citation statements)

References 50 publications

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“…This could therefore be an opportunity to contribute to the treatment of ICH patients using neuroprotectant drugs. Recently, argatroban, a thrombin inhibitor, has shown positive effects in reducing secondary brain damage in a rat ICH model[18]. Up to now, the efficacy and safety of neuroprotectant drugs has only been tested in patients with ICH in subgroup analyses from the CLASS study [19, 20] and from the GAIN studies [21], despite experimental data.…”

Section: Discussionmentioning

confidence: 99%

Citicoline in Intracerebral Haemorrhage: A Double-Blind, Randomized, Placebo-Controlled, Multi-Centre Pilot Study

Secades

Ðlvarez-Sabín²,

Rubio

et al. 2006

Cerebrovasc Dis

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Background: In experimental models citicoline has shown beneficial effects in intracerebral haemorrhage. Citicoline is a neuroprotectant drug with some beneficial effects in human ischaemic stroke and with an excellent safety profile. We decided to carry out a pilot study to test its safety and efficacy in human intracerebral haemorrhaging. Methods: In this double-blind, placebo-controlled pilot study, patients had to be previously independent, aged between 40 and 85 years, and had to be admitted within 6 h after onset of symptoms of an acute primary supratentorial hemispheric cerebral haemorrhage diagnosed by neuroimaging (CT or MRI). Baseline severity was defined as patients with a score larger than 8 points on the Glasgow Coma Scale and larger than 7 on the National Institutes of Health Stroke Scale. Patients received either a placebo or 1 g/12 h citicoline for 2 weeks (orally or intravenously). The primary aim was to evaluate safety with respect to the number of adverse events that occurred. The efficacy endpoint was the percentage of patients with a modified Rankin Score (mRS) at 3 months. Results: 19 patients in each group were included in the study. The incidence of serious adverse events was not different among groups (4 patients in each group). One patient in the placebo group was categorised as independent (mRS ≤ 2) in comparison with 5 patients in the citicoline group (OR, 5.38; 95% CI, 0.55–52). Conclusions: Citicoline seems to be a safe drug in human intracerebral haemorrhage with a positive trend regarding efficacy. These data should be confirmed in a larger trial.

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Section: Discussionmentioning

confidence: 99%

Citicoline in Intracerebral Haemorrhage: A Double-Blind, Randomized, Placebo-Controlled, Multi-Centre Pilot Study

Secades

Ðlvarez-Sabín²,

Rubio

et al. 2006

Cerebrovasc Dis

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“…This study investigated the effects of argatroban, a thrombin inhibitor, on brain edema and inflammation in a rat ICH model. Systemic administration of argatroban reduced secondary brain damage including edema and inflammation [17].…”

Section: Brain Damage After Intracerebral Hemorrhagementioning

confidence: 97%

Latest advances in intracerebral hemorrhage

Ribó¹,

Grotta

2006

Curr Neurol Neurosci Rep

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Despite the fact that intracerebral hemorrhage (ICH) is the deadliest and least treatable of all stroke subtypes, historically researchers have directed most of their efforts toward ischemic strokes. However in the past few years this tendency has been changing, and several studies are showing very interesting results that allow us to believe that in the following years ICH management will change dramatically, paralleling the recent revolution that ischemic stroke treatment experienced in the past decade. Studies offering a better understanding of risk factors, pathophysiology, and treatment will help in primary and secondary prevention and also in developing therapeutic strategies to reduce brain damage. This review comments on some of the most relevant publications during the past year in any field related to ICH.

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“…In the autologous whole-blood rat model, Sun et al 74 demonstrated that hirudin, a direct thrombin inhibitor, was found to decrease perihematomal edema significantly through presumed downregulation of aquaporin-4 and aquaporin-9. In the rat collagenase model, Nagatsuna et al 49 found that systemic administration of argatroban, an inhibitor of free and clot-bound thrombin, reduced edema and neutrophil/monocyte infiltration. Delayed argatroban administration also reduced edema.…”

Section: Therapies Under Investigationmentioning

confidence: 99%

“…51 Importantly, rebleeding in collagenase models was not potentiated by any of the thrombin inhibitors, because treatment and control groups had similar hematoma volumes. 41,49,51 The success of delayed administration suggests a therapeutic window. 51 Although these results are promising, they are not correlated with functional outcome.…”

Section: Therapies Under Investigationmentioning

confidence: 99%

Emerging experimental therapies for intracerebral hemorrhage: targeting mechanisms of secondary brain injury

Belur

Chang²,

He³

et al. 2013

FOC

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Intracerebral hemorrhage (ICH) is associated with a higher degree of morbidity and mortality than other stroke subtypes. Despite this burden, currently approved treatments have demonstrated limited efficacy. To date, therapeutic strategies have principally targeted hematoma expansion and resultant mass effect. However, secondary mechanisms of brain injury are believed to be critical effectors of cell death and neurological outcome following ICH. This article reviews the pathophysiology of secondary brain injury relevant to ICH, examines pertinent experimental models, and highlights emerging therapeutic strategies. Treatment paradigms discussed include thrombin inhibitors, deferoxamine, minocycline, statins, granulocyte-colony stimulating factors, and therapeutic hypothermia. Despite promising experimental and preliminary human data, further studies are warranted prior to effective clinical translation.

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Systemic Administration of Argatroban Reduces Secondary Brain Damage in a Rat Model of Intracerebral Hemorrhage: Histopathological Assessment

Cited by 35 publications

References 50 publications

Citicoline in Intracerebral Haemorrhage: A Double-Blind, Randomized, Placebo-Controlled, Multi-Centre Pilot Study

Citicoline in Intracerebral Haemorrhage: A Double-Blind, Randomized, Placebo-Controlled, Multi-Centre Pilot Study

Latest advances in intracerebral hemorrhage

Emerging experimental therapies for intracerebral hemorrhage: targeting mechanisms of secondary brain injury

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