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Fetal neocortical grafts placed in brain infarcts do not improve paw-reaching deficits in adult spontaneously hypertensive rats.

The aim was to study if neural grafts placed brain infarcts could improve functional recovery. The middle cerebral artery was occluded (MCAO) in 19 spontaneously hypertensive rats. Nine rats were sham operated. Twelve to 16 days after the ischemic insult, 9 of the MCAO rats received transplants of dissociated fetal neocortical tissue (MCAO-T) and 1, 3 and 6 months after transplantation surgery, the rats were behaviorally evaluated by a test for forelimb function. Infarct and transplant sizes were measured morphometrically. The remaining volume of the infarcted hemisphere was 66 +/- 7% (mean +/- SD) in the MCAO group and 71 +/- 9% in the MCAO-T group of the non-operated hemisphere. All grafted rats had surviving transplants. Contralateral to the lesion, paw-reaching was highly impaired in both infarcted groups compared with sham-operated controls with no significant difference between MCAO and MCAO-T. The lesion size correlated significantly with contralateral paw-reach performance at all test periods. We conclude that neocortical grafts did not alleviate the impaired forepaw function.

Animals↗

[Development of new methods in suppressing brain infarction--combined administration of mannitol and perfluorochemicals (author's transl)].

Various therapeutic methods have been attempted for cerebral infarction, but the development of more effective methods is still awaited. We have investigations of the effect of mannitol in preventing the development of cerebral infarction and have reported it effects in clinical cases of operated cerebral aneurysms. In recent years, our attention has been drawn to the so-called red cell substitute, perfluorochemicals (FC), which has a high oxygen-carrying capacity and a small particle less than 0.1 mu. In the present studies, using infarction models in dogs which have previously developed and reported, observations are made on recovery of brain electrical activity in severe ischemia, suppressing brain swelling following recirculation of cerebral blood flow and protection upon the hemorrhagic brain infarction, due to administration of mannitol or FC. These experimental results indicate that the combined administration of mannitol and FC is effective in protecting the brain from cerebral ischemia.

Animals↗

Association of plasma renin activity and echocardiographic left ventricular hypertrophy with frequency of new coronary events and new atherothrombotic brain infarction in older persons with systemic hypertension.

In older hypertensive persons, male gender, prior coronary artery disease, prior atherothrombotic brain infarction (ABI), and echocardiographic left ventricular (LV) hypertrophy are independent risk factors for new coronary events; age, prior ABI, and echocardiographic LV hypertrophy are independent risk factors for new ABI. The data suggest that high plasma renin activity in hypertensive older persons is associated with a high risk of new coronary events and of new ABI through its association with echocardiographic LV hypertrophy.

Aged↗

Tumour necrosis factor-alpha is increased in the cerebrospinal fluid and serum of ischaemic stroke patients and correlates with the volume of evolving brain infarct.

A growing body of evidence suggests the involvement of inflammatory mediators, including cytokines, in the development of ischaemic brain lesions. The aim of the present study was to investigate whether tumour necrosis factor-alpha (TNF-alpha), the proinflammatory cytokine, contributes to early pathophysiological mechanisms leading to brain damage as a consequence of acute stroke. We have studied TNF-alpha levels in cerebrospinal fluid (CSF) and serum in 23 stroke patients within the first 24 hours after ischaemic stroke, confirmed by computerized tomography of the brain (CT). The control group consisted of 15 patients with the diagnosis of tension headache and neurasthenia. In stroke patients the levels of TNF-alpha both in CSF and serum were significantly higher in comparison with the control group. The positive correlation between the levels of TNF-alpha in CSF and serum of the studied patients has been observed. Furthermore, a positive correlation between both TNF-alpha levels in CSF and serum and the volume of evolving brain infarct have been shown.

Adult↗

Segmental arterial spasm in patients with total brain infarction.

An arteriographic investigation has shown that segmental spasm occurs in a relatively high frequency of patients with total brain infarction (12 of 30), and if spasm at the origin of arterial branches is included, the frequency is still higher (19 of 30). The phenomenon is possibly a sign of changed sympathetic tone, the pathophysiological significance of which is discussed.

Adolescent↗

Cellular prion protein is increased in the plasma and peri-infarcted brain tissue after acute stroke.

The physiologic properties of the normal cellular prion protein (PrP(C)) have not been established fully, although recent evidence showed its upregulation in cerebral ischaemia. Using patients, animal models, and in vitro studies we aimed to identify in detail the expression and localization of PrP(C) in ischemic stroke. Patients in acute phase of ischaemic stroke had increased plasma levels of circulating PrP(C) as compared to healthy age- and gender-matched controls (3.1 +/- 1.4 vs. 1.9 +/- 0.7 ng/ml, P = 0.002). Immunohistochemistry showed increased expression of PrP(C) in the soma of peri-infarcted neurones as well as in the endothelial cells (EC) of micro-vessels and inflammatory cells in peri-infarcted brain tissue from patients who survived for 2-34 days after an initial stroke. The same pattern was repeated 1-48 hr after MCAO. RT-PCR showed increased gene expression of PrP(C) by human foetal neurons (HFN) after 12 hr of oxygen glucose deprivation (OGD), which remained increased after 24 hr reperfusion. Western blotting confirmed that protein expression was similarly upregulated, and fluorescent labeling showed a notable increase in peri-nuclear and axonal PrP(C) staining intensity. Increased plasma PrP(C) seems to reflect endogenous expression in acute stroke-affected brain tissue. Increased cellular expression in peri-infarcted regions may influence hypoxia-induced cell damage, although the effects on EC survival and angiogenesis remain to be elucidated.

Acute Disease↗

[Three cases of perioperative brain infarction].

In recent years, the number of elderly patients who require operation has been increasing. We experienced three patients with perioperative brain infarction, occurring respectively, during the preoperative period, just after operation, and three days after operation. All three patients had more than one of the common risk factors for cerebrovascular accidents, including hypertension, advanced age, hyperfibrinogenemia, diabetes mellitus, and past history of cerebrovascular accident. On the basis of our experience with these three patients, we suggest the following: (1) Waiting period of elective surgery should be reconsidered in some cases with a past history of stroke. (2) Some high-risk patients may benefit from anticoagulative or antiaggregative drugs (e.g. low-molecular dextran or prostaglandin E1) to prevent brain ischemia. (3) Abrupt control of hypertension or diabetes mellitus status undoubtedly adversely affects the patient's general condition; and (4) A practical monitoring system to detect regional brain ischemia during operation under general anesthesia should be developed.

Aged↗

[Juvenile-onset multiple brain infarcts localized in the posterior circulation: a case report].

We report a 37-year-old male patient with multiple brain infarcts due to arterial lesions localized in the posterior circulation, who developed a paramedian pontine infarct on the left side. He had been treated as schizophrenia for 20 years. A cranial CT performed one year before showed old small infarcts in the territories of the bilateral thalamo-perforating and left thalamo-geniculate arteries and the right posterior inferior cerebellar artery. The vertebral and basilar arteries were small in diameter on MRI and MR angiography(MRA). Cerebral angiography revealed a narrow smooth basilar artery. In addition, the P2 segments of the bilateral posterior cerebral arteries were markedly narrow with irregular walls. Carotid arteriograms were normal and no atherosclerosis was found. The nature of these arterial lesions remains unknown in this case. Even if MRA shows vertebrobasilar artery hypoplasia, a known congenital risk factor of a posterior circulation infarct, we must rule out a possibility that some arterial pathology is going on.

Adult↗

Determination of S-100 and glial fibrillary acidic protein concentrations in cerebrospinal fluid after brain infarction.

BACKGROUND AND PURPOSE: We initiated the present study to evaluate the clinical value of consecutive concentration determinations of S-100 and glial fibrillary acidic proteins in cerebrospinal fluid from patients with brain infarction. METHODS: We took sequential samples of cerebrospinal fluid from 28 patients within 48 hours, at 7 days, and at 18-21 days after the ictus. We measured astroglial protein concentrations using an enzyme-linked immunosorbent assay and also determined size of the infarction (computed tomography), clinical state of the patient (simplified activities of daily living test), blood-brain barrier dysfunction (cerebrospinal fluid/serum albumin ratio), and a myelin marker (myelin basic protein). RESULTS: We found a transient increase of both proteins in the cerebrospinal fluid during the first week after the ischemic stroke (p less than 0.05). This increment was significantly correlated with the size of the infarction and the clinical state of the patients. CONCLUSIONS: Transient release of astroglial proteins into the cerebrospinal fluid possibly reflects initial focal ischemic damage and, in the later phase, ongoing destruction of astroglial cells in the penumbra zone. We suggest that determinations of cerebrospinal fluid astroglial protein concentrations can be used to estimate ischemic brain damage, which should be of particular value in clinical trials of pharmacological agents, such as calcium antagonists, on stroke patients.

Adult↗

Socioeconomic aspects of postacute care for patients with brain infarction in France.

BACKGROUND: In France, the socioeconomic aspects of stroke have never been addressed. Such analyses are essential for health authorities to justify the establishment of new stroke units when resources are low, provided it can be shown that stroke units are effective in reducing both the morbidity and mortality of stroke. Only 6 dedicated stroke services exist for 60 million inhabitants in France. Our aim was to study acute and postacute pathways and to determine the factors that influence destination after discharge, handicap evolution and costs. METHODS: In a cohort of 494 consecutive patients with brain infarction, we collected information on medical and socioeconomic variables, handicap and its evolution using the modified Rankin scale and Mini-Mental Status score at the 10th day, 6th month and 18th-40th month. These data were recorded during the initial hospital stay, at the follow-up clinic visit and in a home interview done 18-40 months after discharge by research nurses. We used multiple logistic regression for analyses. RESULTS: The most important factor for not returning home was having a Rankin score greater than 3 with an odds ratio of 41.7 (95% confidence interval 19.2-90.0; p = 0.001). Multivariate analysis showed that when the Rankin score was 0, 1 or 2, the main factors for not returning home were socioeconomic variables and serious medical disorders. When the Rankin score was 4 or 5, the main reason for not being sent for rehabilitation was medical status. After adjustment for the Rankin score, patients who returned home or were transferred to rehabilitation were quite similar regarding socioeconomic and medical variables. Other patients transferred to a geriatric ward, nursing home or new housing were more frequently living alone, 60 years of age or older, had less than 2 children, low level of education, dementia or cancer. Overall, the mean cost was 19,513 Euros over an 18-month period and was mainly driven by the level of the Rankin score (e.g. 10,530 vs. 34,809 Euros for Rankin scores of 0-1 and 4-5, respectively). CONCLUSION: These data showed that not only handicap level but also socioeconomic variables are important in determining the destination of stroke patients after discharge. They may help health authorities to make decisions to establish new approaches to treat stroke. This study can also serve as a basis for future cost-effectiveness studies of new drugs being evaluated in therapeutic trials or of new management strategies of stroke patients.

Adolescent↗

Hyperglycaemia protects against neuronal injury around experimental brain infarcts.

Regional glucose utilization was measured in the rat brain after occlusion of the middle cerebral artery. Normoglycaemic rat had increased glucose use in the cerebral cortex adjacent to the infarct. A fraction of the nerve cells were irreversibly injured in this region. In hyperglycaemic rats, the glucose metabolism remained normal and no nerve cell loss was found around the infarct. The findings indicate that hyperglycaemia protects against nerve cell injury in the areas next to experimental brain infarcts.

Animals↗

Recent ischemic brain infarcts at computed tomography: appearances pre- and postcontrast infusion.

Thirty-seven cranial computed tomography (CCT) scans of proved or highly probable recent ischemic brain infarcts were analyzed visually and numerically, with results organized by infarct age. The lesions typically appeared as homogeneous low density abnormalities, with no significant difference in scan characteristics between infarct age groups, i.e., it was not possible to determine the age of an infarct by its noninfused, CCT appearance alone. Eight infarcts showed "mass effect," and 4 of the 20 contrast-infused cases demonstrated marked density augmentation of "blush," indicating that infarcts may resemble tumor in both of these properties.

Adolescent↗

Clinical factors adversely affecting early outcome after brain infarction.

PURPOSE AND METHODS: One-hundred-and-nine consecutive patients admitted during the acute phase of a CT-confirmed brain infarction (BI) were studied. Putative adverse influence of demographic and stroke risk factors, previous medical history, clinical presentation, initial and follow-up neurological examination, initial general evaluation, laboratory findings, chest X-ray and electrocardiographic findings, treatment, and topography and etiology of the ischemic insult was analysed. The end-point for assessment was early death (within 30 days). Statistical analysis was performed with univariate analysis and multiple regression. RESULTS: The main adverse factors related to an increased death risk during the first 30 days were, in decreasing order of importance: coma 48-72 hours after admission; stroke occurring in already hospitalized patients; Babinski sign on admission; minor degrees of impairment of consciousness 48-72 hours after admission; stroke related to large artery atherothrombosis and to embolism; a history of early impairment of consciousness; cardiac failure on admission. In 53 lucid patients on admission, only a history of congestive heart failure (CHF) was associated with a reduced survival rate. In 56 patients with impaired consciousness, the presence of a Babinski sign increased death risk, but the main factor predicting a high case-fatality rate was the persistence of consciousness disturbances after 48-72 hours. CONCLUSIONS: The presence of impairment of consciousness, especially coma, 2-3 days after disease onset, and a history of CHF greatly increase the early case fatality rate in patients with acute BI presenting with or without consciousness disturbances at admission, respectively. The use of a prognostic algorythm considering these few variables seems to predict the approximate 30-day fatality rates.

Adult↗

[A study of the hereditary susceptibility of HLA-DQA1 to essential hypertension, athrothrombotic brain infarction and lacunar stroke].

OBJECTIVE: To study the types of HLA-DQA1 alleles in patients with essential hypertension (EH), athrothrombotic brain infarction (ABI) and lacunar stroke (LS) and normal control individuals and the hereditary susceptibility of HLA-DQA1 alleles to those diseases. METHODS: The allelic typing of HLA-DQA1 was detected by PCR-SSP in 155 cases of EH, ABI and LS and 64 normal individuals. RESULTS: The frequencies of HLA-DQA1 * 0301 in EH, ABI and LS groups were obviously higher than that in normal control group (33.6538 vs. 17.9688, 36.5884 vs. 17.9688, 33.0645 vs. 17.9688, P < 0.01). The frequencies of HLA-DQA1 * 0103 in groups of EH, ABI, LS, ABI with EH, and LS with EH were lower than that in the normal control group (6.7308 vs17.1875, RR = 0.3916, P < 0.01; 6.0976 vs. 17.1875, RR = 0.3548, P < 0.05; 6.4566 vs17.1875, RR = 0.3754, P < 0.01; 2.3809 vs17.1875, RR = 0.1385, P < 0.01; 3.5714 vs. 17.1875, RR = 0.2078, P < 0.01. CONCLUSION: HLA-DQA1 * 0301 allele may be a correlative gene with hereditary susceptibility of EH, ABI and LS, and HLA-DQA1 * 0103 allele may be a protective gene of those diseases.

Adult↗

Effects of perindopril-based blood pressure lowering and of patient characteristics on the progression of silent brain infarct: the Perindopril Protection against Recurrent Stroke Study (PROGRESS) CT Substudy in Japan.

Controversy persists as to whether reducing the blood pressure of patients with a history of stroke leads to an increased risk of silent brain infarct (SBI) and dementia. A total of 667 patients were randomized to receive the angiotensin-converting enzyme (ACE) inhibitor perindopril (4 mg daily), with or without the diuretic indapamide (2 mg daily) or matching placebo(s). Brain CT scanning was performed annually over the mean follow-up period of 3.9 years. Active treatment reduced the blood pressure (systolic/diastolic) by 5.2/2.6 mmHg over the follow-up period. A total of 119 new SBI were detected and 92% of them were lacunar type small infarcts. The frequency of reaching the primary end-point (recurrent symptomatic stroke or new SBI) was similar in the placebo group (26.5%) and in the active treatment group (25.9%). There was no significant difference in brain atrophy indices between two groups. In the subgroup with a history of large artery infarction, 7 out of 55 patients from the placebo group developed new SBI, while none of the 40 patients from the active treatment group did so (p = 0.020). The baseline diastolic blood pressure was significantly associated with the risk of new SBI (p = 0.004), but the stroke subtype was not. In conclusion, blood pressure-lowering with a perindopril-based regimen did not increase the risk of SBI and brain atrophy in patients with a history of stroke. The baseline diastolic blood pressure was an independent predictor of new SBI, but the index stroke subtype did not influence the risk of SBI.

Aged↗

Increased plasma homocysteine is an independent predictor of new atherothrombotic brain infarction in older persons.

A prospective study investigated the association of plasma homocysteine and other risk factors with the incidence of atherothrombotic brain infarction (ABI) at 31 +/- 9 month follow-up in 153 men and 347 women (mean age 81 +/- 9 years, median age 82). The stepwise Cox regression model showed that significant independent predictors of new ABI in older persons were age (risk ratio 1.060 for each 1-year increase of age), plasma homocysteine (risk ratio 1.079 for each 1 micromol/L increase), prior ABI infarction (risk ratio 3.282), current cigarette smoking (risk ratio 2.687), hypertension (risk ratio 2.965), and diabetes mellitus (risk ratio 2.015).

Aged↗

Evaluation of 2,3,5-triphenyltetrazolium chloride staining to delineate rat brain infarcts.

BACKGROUND AND PURPOSE: Accurate and reproducible determination of the size and location of cerebral infarcts is critical for the evaluation of experimental focal cerebral ischemia. The purpose of this study was to compare intracardiac perfusion of 2,3,5-triphenyltetrazolium chloride with immersion of brain tissue in 2,3,5-triphenyltetrazolium chloride to delineate brain infarcts in rats. METHODS: After 6, 24, or 48 hours of ischemia induced by permanent middle cerebral artery occlusion, some rats were perfused with 2,3,5-triphenyltetrazolium chloride; other rats were given an overdose of barbiturates, after which brain sections were immersed in 2,3,5-triphenyltetrazolium chloride. Coronal sections were taken 4, 6, and 8 mm from the frontal pole, and infarct areas in perfused and immersed sections were compared; subsequently, the same sections were stained with hematoxylin and eosin. RESULTS: In rats subjected to 24 or 48 hours of occlusion, areas of infarction were clearly defined with both 2,3,5-triphenyltetrazolium chloride staining techniques, and the infarct sizes correlated well with the results of hematoxylin and eosin staining (r = 0.85-0.94). CONCLUSIONS: These results demonstrate that intracardiac perfusion of 2,3,5-triphenyltetrazolium chloride is an accurate, inexpensive, and efficient staining method to detect infarcted tissue 24 and 48 hours after the onset of ischemia in rats.

Animals↗