Tissue-type plasminogen activator improves neurological functions in a rat model of thromboembolic stroke. 1994

T Sakurama, and R Kitamura, and M Kaneko
Research Laboratories, Sumitomo Pharmaceuticals Co, Ltd, Osaka, Japan.

OBJECTIVE The capacity of an intravenous infusion of double-stranded tissue-type plasminogen activator to salvage neurological functions in a rat model of thromboembolic stroke was studied. METHODS The model of thromboembolic stroke was induced by the intracarotid injection of 2-hour-old homologous blood clots to rats. Neurological functions were scored on a 5-point scale 48 hours after the injection of the clots. Infarction size was determined by triphenyltetrazolium chloride staining, and cerebral hemorrhage was examined macroscopically. RESULTS Intravenous infusion of tissue-type plasminogen activator (1 or 5 x 10(5) IU/kg) within 3 hours after embolization significantly improved neurological functions (P < .01) and reduced infarction size (P < .05). Tissue-type plasminogen activator treatment 6 hours after embolization failed to attenuate the neurological status score. Treatment with tissue-type plasminogen activator did not increase the incidence of intracerebral hemorrhage and was not associated with a systemic fibrinolytic state. In comparison with tissue-type plasminogen activator treatment, although urokinase treatment (5 x 10(5) IU/kg) improved neurological functions, it was associated with a systemic fibrinolytic state and a tendency to increase the incidence of intracerebral hemorrhage. CONCLUSIONS These findings in this model suggest that tissue-type plasminogen activator should be given early after the onset of ischemic symptoms to effectively prevent or limit pathological infarction and improve neurological functions without an increase in the incidence of cerebral hemorrhage.

UI MeSH Term Description Entries
D007262 Infusions, Intravenous The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it. Drip Infusions,Intravenous Drip,Intravenous Infusions,Drip Infusion,Drip, Intravenous,Infusion, Drip,Infusion, Intravenous,Infusions, Drip,Intravenous Infusion
D008297 Male Males
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D010959 Tissue Plasminogen Activator A proteolytic enzyme in the serine protease family found in many tissues which converts PLASMINOGEN to FIBRINOLYSIN. It has fibrin-binding activity and is immunologically different from UROKINASE-TYPE PLASMINOGEN ACTIVATOR. The primary sequence, composed of 527 amino acids, is identical in both the naturally occurring and synthetic proteases. Alteplase,Plasminogen Activator, Tissue-Type,T-Plasminogen Activator,Tissue-Type Plasminogen Activator,Actilyse,Activase,Lysatec rt-PA,TTPA,Tisokinase,Tissue Activator D-44,Lysatec rt PA,Lysatec rtPA,Plasminogen Activator, Tissue,Plasminogen Activator, Tissue Type,T Plasminogen Activator,Tissue Activator D 44,Tissue Type Plasminogen Activator
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D002542 Intracranial Embolism and Thrombosis Embolism or thrombosis involving blood vessels which supply intracranial structures. Emboli may originate from extracranial or intracranial sources. Thrombosis may occur in arterial or venous structures. Brain Embolism and Thrombosis,Cerebral Embolism and Thrombosis,Embolism and Thrombosis, Brain
D002543 Cerebral Hemorrhage Bleeding into one or both CEREBRAL HEMISPHERES including the BASAL GANGLIA and the CEREBRAL CORTEX. It is often associated with HYPERTENSION and CRANIOCEREBRAL TRAUMA. Brain Hemorrhage, Cerebral,Cerebral Parenchymal Hemorrhage,Hemorrhage, Cerebral,Intracerebral Hemorrhage,Hemorrhage, Cerebrum,Brain Hemorrhages, Cerebral,Cerebral Brain Hemorrhage,Cerebral Brain Hemorrhages,Cerebral Hemorrhages,Cerebral Parenchymal Hemorrhages,Cerebrum Hemorrhage,Cerebrum Hemorrhages,Hemorrhage, Cerebral Brain,Hemorrhage, Cerebral Parenchymal,Hemorrhage, Intracerebral,Hemorrhages, Cerebral,Hemorrhages, Cerebral Brain,Hemorrhages, Cerebral Parenchymal,Hemorrhages, Cerebrum,Hemorrhages, Intracerebral,Intracerebral Hemorrhages,Parenchymal Hemorrhage, Cerebral,Parenchymal Hemorrhages, Cerebral
D002544 Cerebral Infarction The formation of an area of NECROSIS in the CEREBRUM caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., INFARCTION, ANTERIOR CEREBRAL ARTERY), and etiology (e.g., embolic infarction). Anterior Choroidal Artery Infarction,Cerebral Infarct,Infarction, Cerebral,Posterior Choroidal Artery Infarction,Subcortical Infarction,Cerebral Infarction, Left Hemisphere,Cerebral Infarction, Right Hemisphere,Cerebral, Left Hemisphere, Infarction,Cerebral, Right Hemisphere, Infarction,Infarction, Cerebral, Left Hemisphere,Infarction, Cerebral, Right Hemisphere,Infarction, Left Hemisphere, Cerebral,Infarction, Right Hemisphere, Cerebral,Left Hemisphere, Cerebral Infarction,Left Hemisphere, Infarction, Cerebral,Right Hemisphere, Cerebral Infarction,Right Hemisphere, Infarction, Cerebral,Cerebral Infarctions,Cerebral Infarcts,Infarct, Cerebral,Infarction, Subcortical,Infarctions, Cerebral,Infarctions, Subcortical,Infarcts, Cerebral,Subcortical Infarctions
D003128 Coma A profound state of unconsciousness associated with depressed cerebral activity from which the individual cannot be aroused. Coma generally occurs when there is dysfunction or injury involving both cerebral hemispheres or the brain stem RETICULAR FORMATION. Comatose,Pseudocoma,Comas,Pseudocomas

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