ABSTRACT
Previous research suggests that the noradrenergic system modulates flexibility of access to the lexical-semantic network, with propranolol benefiting normal subjects in lexical-semantic problem solving tasks. Patients with Broca's aphasia with anomia have impaired ability to access appropriate verbal output for a given visual stimulus in a naming task. Therefore, we tested naming in a pilot study of chronic Broca's aphasia patients with anomia after propranolol and after placebo in a double-blinded crossover manner. Naming was better after propranolol than after placebo, suggesting a potential benefit from propranolol in chronic Broca's aphasia with anomia. Larger follow-up studies are necessary to further investigate this effect.
Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Anomia/drug therapy , Aphasia, Broca/drug therapy , Association Learning/drug effects , Names , Propranolol/therapeutic use , Aged , Analysis of Variance , Anomia/etiology , Anomia/physiopathology , Aphasia, Broca/complications , Aphasia, Broca/etiology , Humans , Language Tests , Middle Aged , Neuropsychological Tests , Reaction Time/drug effects , Stroke/complicationsABSTRACT
OBJECTIVE: We sought to determine clinical predictors of vascular occlusion in patients with stroke. METHODS: From November 1994 to December 1999, 88 patients who were thrombolytic candidates and seen within 6 hours of stroke symptom onset had cerebral angiography. The Oxford Community Stroke Project clinical classification system, admission National Institutes of Health Stroke Scale score, and time from symptom onset until angiography were used to predict vascular occlusion. RESULTS: In all, 79% of patients with total anterior circulation infarctions and 73% with partial anterior circulation infarctions had vascular occlusions, whereas only 29% with lacunar infarcts had occlusion. Strokes were more severe in patients with occlusion than in those without occlusion. Time to angiography was also associated with vascular occlusion. CONCLUSIONS: Clinical classification of stroke, stroke scales, and time to angiography are useful screening tools to predict cerebral occlusion in acute stroke patients.
ABSTRACT
BACKGROUND AND PURPOSE: The current work is based on our previous finding that in neuronal cells, nmol/L concentrations of alpha-tocotrienol (TCT), but not alpha-tocopherol (TCP), blocked glutamate-induced death by suppressing early activation of c-Src kinase and 12-lipoxygenase. METHODS: The single neuron microinjection technique was used to compare the neuroprotective effects of TCT with that of the more widely known TCP. Stroke-dependent brain tissue damage was studied in 12-Lox-deficient mice and spontaneously hypertensive rats orally supplemented with TCT. RESULTS: Subattomole quantity of TCT, but not TCP, protected neurons from glutamate challenge. Pharmacological as well as genetic approaches revealed that 12-Lox is rapidly tyrosine phosphorylated in the glutamate-challenged neuron and that this phosphorylation is catalyzed by c-Src. 12-Lox-deficient mice were more resistant to stroke-induced brain injury than their wild-type controls. Oral supplementation of TCT to spontaneously hypertensive rats led to increased TCT levels in the brain. TCT-supplemented rats showed more protection against stroke-induced injury compared with matched controls. Such protection was associated with lower c-Src activation and 12-Lox phosphorylation at the stroke site. CONCLUSIONS: The natural vitamin E, TCT, acts on key molecular checkpoints to protect against glutamate- and stroke-induced neurodegeneration.
Subject(s)
Antioxidants/pharmacology , Neuroprotective Agents/pharmacology , Vitamin E/analogs & derivatives , Animals , Arachidonate 12-Lipoxygenase/metabolism , Brain/pathology , CSK Tyrosine-Protein Kinase , Cell Death , Cell Line , Cell Survival , Cells, Cultured , Cerebral Cortex/embryology , Fluoresceins , Glutamic Acid/chemistry , Glutamic Acid/metabolism , Hippocampus/cytology , Immunohistochemistry , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Neurons/metabolism , Organic Chemicals/pharmacology , Phosphorylation , Protein-Tyrosine Kinases/metabolism , Proto-Oncogene Proteins pp60(c-src)/metabolism , Random Allocation , Rats , Rats, Inbred SHR , Stroke/metabolism , Stroke/pathology , Time Factors , Tocotrienols , Transfection , Tyrosine/chemistry , Vitamin E/chemistry , Vitamin E/metabolism , Vitamin E/pharmacology , src-Family Kinases/metabolismABSTRACT
BACKGROUND AND PURPOSE: Information about the prognosis of patients with acute ischemic stroke and normal angiography is limited. We report clinical and imaging outcomes of patients seen within 6 hours of symptom onset who were considered candidates for thrombolysis. METHODS: Between November 1994 and December 1999, patients with stroke onset of less than 6 hours who were thrombolytic candidates underwent cerebral angiography. Patients with normal angiograms (defined as no sign of occlusive disease in the head or neck in the symptomatic artery) were included. Admission National Institutes of Health Stroke Scale (NIHSS) scores and discharge modified Rankin scores (mRS) were obtained. CT or MR images were obtained 24 hours or longer after symptom onset. Good outcome was defined as an mRS score < or =2. For analysis, follow-up CT or MR imaging findings were classified as showing cortical infarct, subcortical infarct > or =1.5 cm, subcortical infarct < or =1.5 cm, or no new infarct. The mechanism of the normal angiogram was assumed on the basis of these results. RESULTS: Twenty-one patients with stroke had normal angiograms. About 43% (9/21) of the patients had a favorable hospital discharge clinical outcome, and an additional 33% (7/21) had favorable clinical outcomes at subsequent follow-up. New infarct on follow-up imaging was seen in 71% (15/21). Discharge mRS scores were not correlated with admission NIHSS scores or the mechanism of the normal angiogram. CONCLUSION: Approximately 76% of acute stroke patients with normal angiograms have a favorable clinical outcome, and 71% have associated new infarctions. Given these outcomes, further study is needed before recommendations regarding thrombolytic treatment can be made in this population.
