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PubMed1992

Effect of MK-801 on focal brain infarction in normotensive and hypertensive rats.

The effects of the noncompetitive N-methyl-D-aspartate antagonist MK-801 on infarct size and systemic variables after middle cerebral artery occlusion in spontaneously hypertensive and Fischer-344 rats were investigated. Two doses (0.5 and 5 mg/kg) administered before the induction of ischemia were studied. MK-801 significantly reduced the neocortical volume of infarction (by about 32% at both doses) in Fischer-344 rats and had no neuroprotective effects in the striatum. In contrast, MK-801 had no significant influence on either cortical or striatal infarcted volume in spontaneously hypertensive rats. The reduction or lack of MK-801-induced neuroprotection in spontaneously hypertensive rats, as compared with Fischer-344 rats, could be attributed to a reduced collateral supply in the marginal area due to difference in the morphology of the pial anastomoses and/or in the effects of ischemia and treatment on arterial pressure. The results may have major clinical implications since a great proportion of human strokes are associated with hypertension.

Animals↗
PubMedDate not supplied

Aggregation of multiple risk factors for stroke in siblings of patients with brain infarction and transient ischemic attacks.

Hypertension, heart disease, and diabetes are not only the major risk factors for stroke, but they tend to cluster in families. It is unknown, however, whether these conditions occur more frequently among relatives of patients with specific types of stroke as compared to non-relatives. The frequencies of stroke and its major risk factors in two groups of subjects were compared. One group consisted of 76 siblings of 41 patients hospitalized with cerebral infarction and transient ischemic attacks in an investigative stroke unit; the other consisted of 55 siblings of the patients' spouses. The occurrence of these conditions in the relatives was determined from a questionnaire completed by the relatives and supported by information from the relatives' family physicians. When considered separately, hypertension, heart disease, and stroke occurred in a small but not statistically significant excess among the relatives in-law. However, various combinations of two or three diseases, (including diabetes), occurred in 20.9% of the patients' siblings as compared to only 3.6% of the relatives in-law (p less than 0.001). These results suggest that living siblings of patients with cerebral infarction and transient ischemic attacks may have an increased risk of stroke and cardiovascular disease as a result of multiple risk factors operating simultaneously. Prevention programs among this high risk population may be particularly worthwhile.

Aged↗
PubMed1993

Paw-reaching, sensorimotor, and rotational behavior after brain infarction in rats.

BACKGROUND AND PURPOSE: Functional tests that are stable and consistent over time are an advantage for long-term evaluation of treatment in experimental stroke research. Because little information on this subject is available in rodents with focal cerebral ischemia, we investigated the outcome of three behavioral tests for a period of 3 months after the insult. METHODS: Spontaneously hypertensive rats were sham-operated (n = 27) or underwent an occlusion (n = 36) of the right middle cerebral artery. Before surgery all rats were tested for amphetamine-induced rotational behavior, and half of the rats were trained in a paw-reaching task. One, 2, and 3 months after surgery the tests were repeated, together with a test for sensorimotor function. Infarct size was measured morphometrically. RESULTS: In the lesion group, total hemisphere area was reduced by 22%, caudate putamen by 47%, and the thalamus by 24%. Contralateral to the lesion, paw-reaching was highly impaired, regardless of whether or not the rats had been pretrained, and lesion size correlated significantly to paw-reach performance. Ipsilateral rotation increased and sensorimotor function recovered with time in infarcted rats. CONCLUSIONS: In contrast to amphetamine-induced rotation and sensorimotor behavior, the paw-reaching test provides a stable behavioral parameter after a middle cerebral artery occlusion. Moreover, the lesion-induced deficit in paw-reaching is highly correlated to the extent of the infarct, suggesting that this test is useful in evaluating treatment effects for a longer period of time.

Amphetamine↗
PubMed1997

Incomplete brain infarction of reperfused cortex may be quantitated with iomazenil.

BACKGROUND AND PURPOSE: [123I]Iomazenil is a specific radioligand for the central benzodiazepine receptor that may be useful as an indicator of the intactness of cortical neurons after focal cerebral ischemia. We evaluated the binding of this receptor in reperfused cortex among patients with ischemic stroke to detect viable neurons in cortex that appeared structurally intact on conventional neuroimaging studies. METHODS: Fourteen patients were selected by (1) angiography within 24 hours of onset showing embolic occlusion of an intracranial artery, (2) cerebral blood flow showing ischemia of moderate severity in 12 cases and spontaneous reflow in 2 cases, and (3) thrombolysis with reperfusion within 24 hours in most cases. Thirty reperfused cortical areas that remained structurally intact, 7 infarcted cortical areas, and 6 contralateral cerebellar areas with reduced blood flow were selected as regions of interest to estimate receptor binding 5 days to 23 months after the stroke. A two-compartment model was used to compute the distribution volume (Vd) of iomazenil in relative units, with Vd proportional to benzodiazepine receptor concentration. The side-to-side asymmetry ratio of Vd was calculated. RESULTS: The mean asymmetry ratio was 0.89 +/- 0.11 (range, 0.64 to 1.05), 0.50 +/- 0.15 (range, 0.23 to 0.67), and 0.97 +/- 0.05 (range, 0.90 to 1.04) in reperfused cortex, infarcted cortex, and contralateral cerebellum, respectively. Compared with unity, both reperfused cortex and infarcted cortex showed significant decrease of Vd (P < .001). Contralateral cerebellum showing diaschisis had no reduction of Vd. On MRI, obtained 3 or 6 months after the stroke, mild cortical atrophy was observed in two reperfused areas where the asymmetry ratio was moderately reduced (0.64 and 0.80). CONCLUSIONS: The reduction of benzodiazepine receptor concentration in reperfused cortex that remained structurally intact is likely to be the result of injury involving only a limited number of neurons (ie, incomplete infarction). Our data suggest that the degree of viability of ischemic cortex apparently salvaged by early reperfusion can be quantified by iomazenil.

Aged↗
PubMed1999

Contrast-enhanced transcranial color-coded sonography in acute hemispheric brain infarction.

PURPOSE: The aim of the present study was to investigate the diagnostic potential of contrast-enhanced transcranial color-coded real-time sonography (CE-TCCS) in otherwise ultrasound-refractory acute stroke patients with an ischemia in the territory of the middle cerebral artery (MCA). Furthermore, correlations of CE-TCCS findings with clinical, angiographic, and CT results were investigated. METHODS: In 90 acute stroke patients with inadequate insonation conditions in unenhanced transcranial color-coded real-time sonography (TCCS) examinations, CE-TCCS, clinical, angiographic, and CT examinations were performed within 12 hours, 36 hours (CE-TCCS only), and 1 week after onset of clinical symptoms. A CT angiography (CTA) as reference method was available in 39 individuals. After application of a galactose-based echo-enhancing agent, the portion of conclusive ultrasound examinations of the MCA, as manifested by an MCA occlusion, decreased or increased flow velocity (FV), and symmetrical MCA FV, was evaluated. CE-TCCS findings on admission and during follow-up were correlated with infarction size as demonstrated on follow-up CT, and clinical findings were assessed by use of the European Stroke Scale. RESULTS: Adequate diagnosis was achieved in 74 of 90 patients (82%) by the use of echo contrast agents. MCA occlusion or reduction of MCA FV was found in 20 and 27 patients, respectively. MCA occlusion was confirmed by CTA in 17 cases. In one individual, false-positive diagnosis of MCA occlusion was made according to ultrasound criteria. In 5 patients with MCA occlusion, vessel recanalization was observed during follow-up; 15 of 27 patients with decreased flow velocities showed normalization after the third examination that was associated with a significantly better clinical outcome (P<0.0001). Furthermore, MCA occlusion or decreased FV in the first 12 hours were associated with significantly larger infarctions in the MCA territory compared with normal CE-TCCS findings (P<0.0001). CONCLUSIONS: CE-TCCS enables adequate diagnosis in approximately 80% of acute hemispheric stroke patients with insufficient unenhanced TCCS examinations. It is a reliable diagnostic tool regarding MCA mainstem and branch occlusions. Because this method conveys useful information concerning cerebral tissue and clinical prognosis, it may be useful to identify those patients who benefit most from local or intra-arterial thrombolytic therapy.

Acute Disease↗
PubMed1983

Can ethanol intoxication affect hemocoagulation to increase the risk of brain infarction in young adults?

We studied the effects of acute ethanol intoxication on platelet function, coagulation factors, and fibrinolytic activity in 12 healthy men. During the ethanol session, 10 of the 12 developed a transient decrease in fibrinolytic activity. Ethanol ingestion increased factor VIII coagulant activity. VIII-related antigen, and VIII-ristocetin cofactor. The highest levels were detected 16 hours after beginning ethanol ingestion (p less than 0.001), and the bleeding time decreased at 12 hours (p less than 0.01). Ethanol had no effects on platelet count, beta-thromboglobulin, antithrombin III, ethanol gelation, or fibrin/fibrinogen degradation products. Decreased fibrinolytic activity, increased factor VIII complex, and shortened bleeding time may explain why ethanol intoxication increases susceptibility to cerebral thrombosis.

Adult↗
PubMed1992

Type and extent of hemispheric brain infarctions and clinical outcome in early and delayed middle cerebral artery recanalization.

We evaluated the influence of time of recanalization or degree of initial leptomeningeal collateral blood flow in cardioembolic or arterio-arterial middle cerebral artery (MCA) occlusion on infarct size and clinical outcome in a series of 34 consecutive acute stroke patients with main stem (N = 31) or major branch (N = 3) occlusions using CT, initial cerebral arteriography (N = 21), repetitive close-meshed transcranial Doppler ultrasonography, and a neurologic stroke scale. We treated 15 patients with tissue plasminogen activator intravenously within the first 6 hours. The type and size of infarction depended on the location of the occluding lesions within the MCA trunk. Proximal MCA occlusion always led to infarction involving the striatum and internal capsule. Sixty-five percent of patients showed recanalization of the occluded MCA within 1 week. Following MCA recanalization, hyperperfusion was present in 38 to 44% of cases. There was a marginally significant relation between size of infarction on CT and recanalization time within the first 24 hours. The more rapidly recanalization occurred, the smaller the size of the infarct. When recanalization time was greater than 8 hours, the lesions always extended to the cortex. An additional good leptomeningeal collateral blood flow significantly reduced the size of the infarct and improved clinical outcome after 17 days and after 10 months. Early recanalization of embolic MCA occlusions within up to 8 hours, in conjunction with good transcortical collateralization, has a favorable impact on infarct size and outcome and may constitute the therapeutic window of opportunity.

Aged↗
PubMed1993

Brain infarction severity differs according to cardiac or arterial embolic source.

We compared clinical and radiologic features between 246 cardiac embolism (EMB) and 66 arterial embolic (tandem arterial pathology [TAP]) patients selected from the 1,273 patients with cerebral infarction in the Stroke Data Bank. Diagnostic definitions accounted for the increased frequency of cardiac disease among patients with EMB compared with TAP (78.4% versus 29.3%), while transient ischemic attacks (32.3% versus 13.1%) and carotid artery bruit (15.1% versus 3.3%) were more prevalent in TAP than in EMB. Multiple logistic regression differentiated TAP and EMB further. The probability of a TAP diagnosis was increased by the CT finding of a superficial infarct alone (odds ratio [OR] = 4.6; 95% CI = 1.5 to 13.7) or by a higher admission hematocrit. The probability of EMB was greater in patients with an initial decreased consciousness (OR = 39.2; 95% CI = 4.0 to 381.3) or with an abnormal first CT (OR = 3.2; 95% CI = 1.2 to 8.6). These findings indicate that the two infarct subtypes differ in the location and extent of the cortical infarction, which argues for a smaller particle size, with smaller and more distal infarction in embolism from an arterial source compared with cardiogenic embolism.

Aged↗
PubMed1997

The common MELAS mutation A3243G in mitochondrial DNA among young patients with an occipital brain infarct.

The syndrome of mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) may present with symptoms that resemble a stroke. The strokelike episodes most commonly involve the posterior part of the cerebrum. We identified retrospectively 38 patients with an occipital stroke between ages 18 to 45 years during a 19-year period in a hospital serving as the only neurologic center for a specific population. The common MELAS mutation at the base pair 3243 (A3243G) of the mitochondrial DNA (mtDNA) was analyzed in blood samples. We found four patients (10%) with a clinical or molecular diagnosis of a mitochondrial disorder. Two of the patients carried the A3243G mutation, suggesting frequencies of 6% among patients younger than 45 years of age and 14% among patients younger than 30 years for this mutation. Furthermore, we identified two patients with a clinically definite mitochondrial disorder, and sequencing of the 22 transfer RNA genes revealed the mtDNA mutation A12308G in one patient. Clinical evaluation revealed that occipital stroke was part of a more complex syndrome in these four patients. These population-based findings demonstrate that the A3243G mutation in the mtDNA, and mitochondrial disorders are not uncommon among young patients with occipital stroke.

Adolescent↗