Tissue-type plasminogen activator improves neurological functions in a rat model of thromboembolic stroke.

Sakurama, Teruo; Kitamura, Ryosuke; Kaneko, Munekiyo

doi:10.1161/01.str.25.2.451

Cited by 18 publications

(8 citation statements)

References 40 publications

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“…Almost equal decreases in CBF were obtained. Neurological scores and cerebral infarction area are also consistent with those obtained from the suture and conventional blood clot embolic model (22,23). All animals exhibited moderate to severe neurological scores and infarction areas 24 h after embolization and a clear infarction area was observed at the cerebral hemisphere affected by embolization.…”

Section: Discussionsupporting

confidence: 84%

A Novel Embolic Model of Cerebral Infarction and Evaluation of Stachybotrys microspora Triprenyl Phenol-7 (SMTP-7), a Novel Fungal Triprenyl Phenol Metabolite

et al. 2010

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Abstract. The aim of the present study was to establish a novel embolic model of cerebral infarction and to evaluate the effect of Stachybotrys microspora triprenyl phenol-7 (SMTP-7), a novel fungal triprenyl phenol metabolite. Thrombotic occlusion was induced by transfer of acetic acid-induced embolus into the brain. The regional cerebral blood flow was measured by a laser Doppler flowmeter to check the ischemic condition. Infarction area was assessed by 2% 2,3,5-triphenyltetrazolium chloride (TTC) staining. Neurological scores were determined by a modified version of the method described by Longa et al. Emboli were accumulated at the temporal or parietal region of the middle cerebral artery. Additionally, we found that this model showed decreased cerebral blood flow and increased infarction area and neurological scores. Treatment with tissue plasminogen activator (t-PA) reduced infarction area and the neurological scores in a dose-dependent manner; moreover, the decreased cerebral blood flow recovered. SMTP-7 also reduced these values. The therapeutic time window of SMTP-7 was longer than that of t-PA. These results indicate that this model may be useful for understanding the pathophysiological mechanisms of cerebral infarction and evaluating the effects of therapeutic agents. Additionally, SMTP-7 is a promising approach to extend the therapeutic time window. Therefore, this novel compound may represent a novel approach for the treatment of cerebral infarction.

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Section: Discussionsupporting

confidence: 84%

A Novel Embolic Model of Cerebral Infarction and Evaluation of Stachybotrys microspora Triprenyl Phenol-7 (SMTP-7), a Novel Fungal Triprenyl Phenol Metabolite

et al. 2010

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“…14 The only partial exception to this is a report by Sakurama et al, 19 in which treatment with tPA as long as 6 hours after stroke significantly reduced lesion development but failed to improve the neurological status of the treated animals. The model or technical distinctions responsible for the various reported treatment windows are not clear but likely reflect thromboembolic model differences in emboli preparation or surgical technique.…”

Section: Discussionmentioning

confidence: 98%

Inhibition of Factor IX(a) Is Protective in a Rat Model of Thromboembolic Stroke

Toomey

Valocik

Koster

et al. 2002

Stroke

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Background and Purpose-Although used clinically to prevent stroke, there are few examples of anticoagulant investigations in the treatment of acute thromboembolic stroke in animal models. The treatment of thromboembolic stroke in experimental models has been investigated almost exclusively around the use of tissue plasminogen activator (tPA). In this study, using a rat thromboembolic stroke model, we investigated the use of an inhibitory anti-factor IX(a) monoclonal antibody (SB 249417) for the treatment of thromboembolic stroke and compared its efficacy to that of tPA. Methods-Stroke was initiated by delivering 6 clots into the internal carotid artery. After 2, 4, or 6 hours, rats received either intravenous vehicle, 10.0 mg/kg tPA, or 1.0, 2.0, or 3.0 mg/kg SB 249417. At 24 hours after stroke, infarct volumes and neurological deficits were assessed. Results-Treatment with tPA 2, 4, or 6 hours after stroke reduced infarct volumes by 35% (PϭNS), 45%, and 39%, respectively. tPA treatment did not improve neurological deficits at any time point. Treatment with SB 249417 (3.0 mg/kg) 2, 4, or 6 hours after stroke reduced infarct volumes by 44%, 50%, and 13% (PϭNS), respectively. Neurological deficits were reduced by 49%, 42%, and 13% (PϭNS), respectively. Neither mortality nor hemorrhage was affected by either treatment. Conclusions-The data indicate that the inhibition of factor IX(a) within 4 hours of thromboembolic stroke produced a more favorable outcome than tPA. When treatment was initiated 6 hours after stroke, the benefits of factor IX(a) inhibition were lost, whereas tPA continued to suppress lesion development, albeit without a corresponding improvement in functional deficits. This study suggests that cerebral ischemia and the resultant perfusion deficit are exacerbated by the activation of blood coagulation and that anticoagulants like SB 249417 may find utility in the treatment of ischemic stroke. (Stroke. 2002;33:578-585.)

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“…Thromboembolic stroke, the most common stroke type in humans, can be mimicked in rodents and used for many purposes: preclinical testing of thrombolytic agents [38][39][40], evaluation of the ischemic lesion under the effect of thrombolysis [41,42], investigation of the consequences of thrombolysis such as hemorrhagic transformation [43], and to test novel antithrombotic agents [44,45] and combination therapies (e.g. thrombolytic agents and neuroprotective drugs) [46][47][48].…”

Section: Focal Cerebral Ischemia Models Thromboembolic Modelmentioning

confidence: 99%

Rodent Models of Ischemic Stroke: A Useful Tool for Stroke Drug Development

Durukan

Strbian²,

Tatlısumak

2008

CPD

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Stroke is the third common cause of death and the most common cause of adult disability. Approximately 80% of all strokes are ischemic (brain infarction). The only approved acute therapy is intravenous thrombolysis with tissue plasminogen activator within 3 h of symptom onset but only a small percentage of all ischemic stroke patients can receive this therapy. Therefore, novel therapeutic approaches directed at the pathophysiological mechanisms involved in ischemic brain injury are urgently needed. To this end several experimental stroke models were developed. These models are indispensable for understanding the pathophysiology of brain ischemia and to develop novel drugs and investigative methodology. This review considers the most commonly used ischemic stroke models (including preconditioning models) in rodents emphasizing their advantages and disadvantages. Since none of the models can perfectly simulate human stroke, researchers must interpret experimental findings carefully.

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Tissue-type plasminogen activator improves neurological functions in a rat model of thromboembolic stroke.

Cited by 18 publications

References 40 publications

A Novel Embolic Model of Cerebral Infarction and Evaluation of Stachybotrys microspora Triprenyl Phenol-7 (SMTP-7), a Novel Fungal Triprenyl Phenol Metabolite

A Novel Embolic Model of Cerebral Infarction and Evaluation of Stachybotrys microspora Triprenyl Phenol-7 (SMTP-7), a Novel Fungal Triprenyl Phenol Metabolite

Inhibition of Factor IX(a) Is Protective in a Rat Model of Thromboembolic Stroke

Rodent Models of Ischemic Stroke: A Useful Tool for Stroke Drug Development

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