| Neuroprotection by excitatory amino acid antagonist augments the benefit of thrombolysis in embolic stroke in rats. | |
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MedLine Citation:
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PMID: 8236347 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND AND PURPOSE: The effects of delayed thrombolysis with alteplase and neuroprotection with an excitatory amino acid receptor antagonist and their combination were tested in an embolic stroke model. METHODS: In 61 rats the carotid artery territory was embolized with arterial-like fibrin-rich clots. Hemispheric cerebral blood flow before and after embolization was measured by intra-arterial 133Xe injection method. The animals were assigned to one of the following treatments: (1) vehicle-treated controls (n = 15); (2) dizocilpine 1 mg/kg i.v. 5 minutes after embolization (n = 16); (3) alteplase 20 mg/kg as an intravenous continuous infusion starting 2 hours after embolization (n = 16); and (4) both agents (n = 14). Carotid angiography displayed the site of occlusion of the cerebral arterial tree immediately after and 3 hours after embolization, and the clinical neurological score was assessed after the rats recovered from anesthesia and before the rats were killed. Brains were fixed after 2 days and evaluated neuropathologically; infarct volume affecting cortical and deep brain structures was measured separately. RESULTS: Both alteplase and dizocilpine reduced the total infarct volume (P = .05 and P = .04, respectively, Mann-Whitney tests). Dizocilpine reduced the incidence of cortical infarctions by 48% (P < .001, Fisher's test). Only the combined treatment significantly reduced deep brain infarctions (P = .03, Mann-Whitney test). The combined treatment also improved the clinical score by 83% compared with controls, by 75% compared with the group treated by dizocilpine alone, and by 50% compared with the group treated by alteplase alone. Sixty-seven percent of thrombolytic-treated animals recanalized completely compared with 39% of those given no thrombolytics (P = .05, Fisher's test). The clinical outcome correlated with infarct size (P < .01, Spearman test). CONCLUSIONS: Our results document comparable efficacy of delayed thrombolysis and excitatory amino acid receptor antagonism in this model and suggest that combination of these two therapeutic approaches may yield additional benefit in treatment of thromboembolic stroke, particularly in cases where deep brain (end-artery-supplied) structures are affected. |
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Authors:
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T Sereghy; K Overgaard; G Boysen |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Stroke; a journal of cerebral circulation Volume: 24 ISSN: 0039-2499 ISO Abbreviation: Stroke Publication Date: 1993 Nov |
Date Detail:
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Created Date: 1993-11-29 Completed Date: 1993-11-29 Revised Date: 2003-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0235266 Medline TA: Stroke Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1702-8 Citation Subset: IM |
Affiliation:
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Department of Neurology, University Hospital of Copenhagen, Rigshospitalet, Denmark. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Pressure / drug effects Brain / pathology* Carbon Dioxide / blood Cerebral Angiography Cerebral Infarction / pathology, physiopathology, prevention & control* Dizocilpine Maleate / therapeutic use* Drug Therapy, Combination Infusions, Intravenous Intracranial Embolism and Thrombosis / drug therapy*, pathology, physiopathology Male N-Methylaspartate / antagonists & inhibitors Oxygen / blood Partial Pressure Rats Rats, Sprague-Dawley Thrombolytic Therapy* Time Factors Tissue Plasminogen Activator / administration & dosage, therapeutic use* |
| Chemical | |
Reg. No./Substance:
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124-38-9/Carbon Dioxide; 6384-92-5/N-Methylaspartate; 77086-22-7/Dizocilpine Maleate; 7782-44-7/Oxygen; EC 3.4.21.68/Tissue Plasminogen Activator |
| Comments/Corrections | |
Erratum In:
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Stroke 1997 Feb;28(2):466 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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