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Cerebrovascular adaptations to cocaine-induced transient ischemic attacks in the rodent brain.

ABSTRACT: Occurrence of transient ischemic attacks (TIA) and cerebral strokes is a recognized risk associated with cocaine abuse. Here, we use a rodent model along with optical imaging to study cocaine-induced TIA and the associated dynamic changes in cerebral blood flow velocity (CBFv) and cerebrovasculature. We show that chronic cocaine exposure in mice resulted in marked cortical hypoperfusion, in significant arterial and venous vasoconstriction, and in a sensitized vascular response to an acute cocaine injection. Starting after 10 days of exposure, an acute cocaine challenge to these mice resulted in a TIA, which presented as hemiparalysis and was associated with an abrupt exacerbation of CBFv. The severity of the TIA correlated with the decreases in cortical CBFv such that the greater the decreases in flow, the longer the TIA duration. The severity of TIA peaked around 17-22 days of cocaine exposure and decreased thereafter in parallel to a reorganization of CBFv from superficial to deep cortical layers, along with an increase in vessel density into these layers. Here, we document for the first time to our knowledge evidence of a TIA in an animal model of chronic cocaine exposure that was associated with profound decreases in CBFv, and we revealed that while the severity of the TIA initially increased with repeated exposures, it subsequently improved in parallel to an increase in the vessel density. This suggests that strategies to accelerate cerebrovascular recovery might be therapeutically beneficial in cocaine abusers.

SUBMITTER: You J

PROVIDER: S-EPMC5333953 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Paroxysmal Hemiballism/Hemichorea Resulting from Transient Ischemic Attacks.

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Cocaine-induced cortical microischemia in the rodent brain: clinical implications.

Project description:Cocaine-induced stroke is among the most serious medical complications associated with its abuse. However, the extent to which acute cocaine may induce silent microischemia predisposing the cerebral tissue to neurotoxicity has not been investigated; in part, because of limitations of current neuroimaging tools, that is, lack of high spatiotemporal resolution and sensitivity to simultaneously measure cerebral blood flow (CBF) in vessels of different calibers (including capillaries) quantitatively and over a large field of view. Here we combine ultrahigh-resolution optical coherence tomography to enable tracker-free three-dimensional (3D) microvascular angiography and a new phase-intensity-mapping algorithm to enhance the sensitivity of 3D optical Doppler tomography for simultaneous capillary CBF quantization. We apply the technique to study the responses of cerebral microvascular networks to single and repeated cocaine administration in the mouse somatosensory cortex. We show that within 2-3 min after cocaine administration CBF markedly decreased (for example, ~70%), but the magnitude and recovery differed for the various types of vessels; arterioles had the fastest recovery (~5 min), capillaries varied drastically (from 4-20 min) and venules showed relatively slower recovery (~12 min). More importantly, we showed that cocaine interrupted CBF in some arteriolar branches for over 45 min and this effect was exacerbated with repeated cocaine administration. These results provide evidence that cocaine doses within the range administered by drug abusers induces cerebral microischemia and that these effects are exacerbated with repeated use. Thus, cocaine-induced microischemia is likely to be a contributor to its neurotoxic effects.

| S-EPMC3934297 | biostudies-literature

Transient ischemic attacks characterized by RNA profiles in blood.

Project description:ObjectiveTransient ischemic attacks (TIA) are common. Though systemic inflammation and thrombosis are associated with TIA, further study may provide insight into TIA pathophysiology and possibly lead to the development of treatments specifically targeted to TIA. We sought to determine whether gene expression profiles in blood could better characterize the proinflammatory and procoagulant states in TIA patients.MethodsRNA expression in blood of TIA patients (n = 26) was compared to vascular risk factor control subjects without symptomatic cardiovascular disease (n = 26) using Affymetrix U133 Plus 2.0 microarrays. Differentially expressed genes in TIA were identified by analysis of covariance and evaluated with cross-validation and functional analyses.ResultsPatients with TIA had different patterns of gene expression compared to controls. There were 480 probe sets, corresponding to 449 genes, differentially expressed between TIA and controls (false discovery rate correction for multiple comparisons, p ≤ 0.05, absolute fold change ≥1.2). These genes were associated with systemic inflammation, platelet activation, and prothrombin activation. Hierarchical cluster analysis of the identified genes suggested the presence of 2 patterns of RNA expression in patients with TIA. Prediction analysis identified a set of 34 genes that discriminated TIA from controls with 100% sensitivity and 100% specificity.ConclusionPatients with recent TIA have differences of gene expression in blood compared to controls. The 2 gene expression profiles associated with TIA suggests heterogeneous responses between subjects with TIA that may provide insight into cause, risk of stroke, and other TIA pathophysiology.

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Transient Ischemic Attacks Preceding Ischemic Stroke and the Possible Preconditioning of the Human Brain: A Systematic Review and Meta-Analysis.

Project description:Stroke is a leading cause of mortality and disability worldwide. Transient ischemic attack (TIA) is defined as transient brain ischemia with temporary neurological deficits. In animal models, prior TIA seems to enhance brain ischemic tolerance to withstand further ischemic events, which might be explained by brain preconditioning. Thus, this review aims to formulate evidence of whether TIAs can induce positive preconditioning and enhance the functional outcomes in patients suffering from subsequent ischemic strokes. Five databases were searched (PubMed, Embase, SAGE, Web of Science, and Scopus), and twelve studies were included in the quantitative analysis. Studies were eligible when comparing patients with acute ischemic stroke (AIS) and previous TIA with those with AIS without TIA. Comparisons included the National Institute of Health Stroke Scale (NIHSS) score at admission and 7 days from the stroke event, modified Rankin score (mRS), and Trial of ORG 10,172 in Acute Stroke Treatment (TOAST) classification. Odds ratio (OR), mean difference (MD), and 95% confidence interval (CI) were used to describe our results using the random effect model. Our results revealed that patients with stroke and prior TIAs had lower NIHSS scores at admission than those without prior TIAs. However, the NIHSS score was not significantly different between the two groups at 7 days. Furthermore, there was no statistically significant difference between both groups in terms of mortality. Despite the differences in the admission mRS score groups, patients with prior TIAs had lower mRS scores at discharge.

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Cerebral hemodynamic failure presenting as limb-shaking transient ischemic attacks.

Project description:Limb-shaking transient ischemic attacks (TIA) may occur in patients with insufficient brain perfusion due to an underlying occlusive disease. We present the case of a 64-year-old patient who suffered from repetitive TIA presenting with shaking movements of the right-sided extremities and accompanying speech arrest. Symptoms are documented in the online supplementary video (www.karger.com/doi/10.1159/000327683). These episodes were frequently triggered in orthostatic situations. The diagnosis of limb-shaking TIA was established. The diagnostic workup revealed pseudo-occlusion of the left internal carotid artery, a poor intracranial collateral status and, as a consequence, an exhausted vasomotor reserve capacity. At ultrasound examination, symptoms were provoked by a change of the patient's position from supine to sitting. During evolvement of symptoms, a dramatic decrease of flow velocities in the left middle cerebral artery was observed. This case thus documents the magnitude and dynamics of perfusion failure in a rare manifestation of cerebral ischemic disease.

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Transient ischemic attacks in patients with active and occult cancer.

Project description:Background and aimParaneoplastic coagulopathy can present as stroke and is associated with specific biomarker changes. Identifying paraneoplastic coagulopathy can help guide secondary prevention in stroke patients, and early cancer detection might improve outcomes. However, unlike ischemic stroke, it remains unclear whether paraneoplastic coagulopathy is associated with transient ischemic attacks (TIA). This study assessed the presence of cancer-related biomarkers in TIA patients and evaluated long-term mortality rates in patients with and without active cancer.MethodsActive cancer was retrospectively identified in consecutive TIA patients treated at a comprehensive stroke center between 2015 and 2019. An association between the presence of cancer and cancer-related biomarkers was assessed using multivariable logistic regression. Long-term mortality after TIA was analyzed using multivariable Cox regression.ResultsAmong 1436 TIA patients, 72 had active cancer (5%), of which 17 were occult (1.2%). Cancer-related TIA was associated with male gender (adjusted odds ratio [aOR] 2.29, 95% CI 1.12-4.68), history of smoking (aOR 2.77, 95% CI 1.34-5.7), elevated D-dimer (aOR 1.77, 95% CI 1.26-2.49), lactate dehydrogenase (aOR 1.003, 95% CI 1.00-1.005), lower leukocyte count (aOR 1.20, 95% CI 1.04-1.38), and lower hemoglobin (aOR 1.02, 95% CI 1.00-1.04). Long-term mortality was associated with both active cancer (adjusted hazard ratios [aHR] 2.47, 95% CI 1.58-3.88) and occult cancer (aHR 3.08, 95% CI 1.30-7.32).ConclusionCancer-related TIA is not uncommon. Biomarkers known to be associated with cancer-related stroke also seem to be present in TIA patients. Early identification would enable targeted treatment strategies and could improve outcomes in this patient population.

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Prevalence, knowledge, and treatment of transient ischemic attacks in China.

Project description:ObjectivesTo investigate the prevalence, knowledge, and treatment of TIA in a Chinese adult population.MethodsWe conducted a complex, multistage, probability sampling-designed, cross-sectional, nationwide survey of 98,658 Chinese adults in 2010. Possible TIA cases were first identified by symptoms recall or self-reported history of TIA through face-to-face interviews, and the final diagnosis was then made by expert neurologists through phone interviews or record review.ResultsThe age-standardized prevalence of TIA was 2.27%. Clinically, only 16.0% of the participants were diagnosed before the study. The prevalence of TIA was higher in women and in patients who were older, had less education, were current smokers, lived in rural or undeveloped areas, and had a history of stroke, hypertension, myocardial infarction, dyslipidemia, or diabetes. Based on the survey responses, approximately 3.08% of Chinese adults had knowledge of TIA. Among patients with TIA, only 5.02% received treatment and 4.07% received guideline-recommended therapy.ConclusionsTIA is prevalent and an estimated 23.9 million people in China may have experienced a TIA. Public knowledge on TIA is very limited. TIA appears to be largely undiagnosed and untreated in China. There is an urgent need to develop strategies to improve the identification and appropriate management of TIA.

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Project description:There is now considerable evidence that Transient Ischemic Attack (TIA) carries important sequelae beyond the risk of recurrent stroke, particularly with respect to peri-event and post-event cognitive dysfunction and subsequent cognitive decline. The occurrence of a TIA could provide an important window in understanding the relationship of early mixed vascular-neurodegenerative cognitive decline, and by virtue of their clinical relevance as a "warning" event, TIAs could also furnish the opportunity to act preventatively not only for stroke prevention but also for dementia prevention. In this review, we discuss the current state of the literature regarding the cognitive sequelae associated with TIA, reviewing important challenges in the field. In particular, we discuss definitional and methodological challenges in the study of TIA-related cognitive impairment, confounding factors in the cognitive evaluation of these patients, and provide an overview of the evidence on both transient and long-term cognitive impairment after TIA. We compile recent insights from clinical studies regarding the predictors and mediators of cognitive decline in these patients and highlight important future directions for work in this area.

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A predictive analytics model for differentiating between transient ischemic attacks (TIA) and its mimics.

Project description:BackgroundTransient ischemic attack (TIA) is a brief episode of neurological dysfunction resulting from cerebral ischemia not associated with permanent cerebral infarction. TIA is associated with high diagnostic errors because of the subjective nature of findings and the lack of clinical and imaging biomarkers. The goal of this study was to design and evaluate a novel multinomial classification model, based on a combination of feature selection mechanisms coupled with logistic regression, to predict the likelihood of TIA, TIA mimics, and minor stroke.MethodsWe conducted our modeling on consecutive patients who were evaluated in our health system with an initial diagnosis of TIA in a 9-month period. We established the final diagnoses after the clinical evaluation by independent verification from two stroke neurologists. We used Recursive Feature Elimination (RFE) and Least Absolute Shrinkage and Selection Operator (LASSO) for prediction modeling.ResultsThe RFE-based classifier correctly predicts 78% of the overall observations. In particular, the classifier correctly identifies 68% of the cases labeled as "TIA mimic" and 83% of the "TIA" discharge diagnosis. The LASSO classifier had an overall accuracy of 74%. Both the RFE and LASSO-based classifiers tied or outperformed the ABCD2 score and the Diagnosis of TIA (DOT) score. With respect to predicting TIA, the RFE-based classifier has 61.1% accuracy, the LASSO-based classifier has 79.5% accuracy, whereas the DOT score applied to the dataset yields an accuracy of 63.1%.ConclusionThe results of this pilot study indicate that a multinomial classification model, based on a combination of feature selection mechanisms coupled with logistic regression, can be used to effectively differentiate between TIA, TIA mimics, and minor stroke.

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Project description:Moyamoya disease (MMD) is a rare cerebro-occlusive disease with unknown etiology that can cause both ischemic and hemorrhagic stroke. MMD is characterized by progressive stenosis of the terminal internal carotid artery (ICA) and development of basal brain collaterals. Early-stage MMD is known to cause hemodynamic insufficiency despite mild or moderate stenosis of the intracranial arteries, but the exact mechanism underlying this pathophysiological condition is undetermined. We used high-resolution Large Eddy Simulations to investigate multiple complex hemodynamic phenomena that led to cerebral ischemia in five patients with early-stage MMD. The effects of transitional flow, coherent flow structures and blood shear-thinning properties through regions of tortuous and stenosed arteries were explored and linked to symptomatology. It is evidently shown that in some cases complex vortex structures, such as Rankine-type vortices, redirects blood flow away from some arteries causing significant reduction in blood flow. Moreover, partial blood hammer (PBH) phenomenon was detected in some cases and led to significant hemodynamic insufficiency. PBH events were attributed to the interaction between shear-thinning properties, transitional flow structures and loss of upstream pressure-velocity phase lag. We clearly show that the hemodynamic complexities in early-stage MMD could induce ischemia and explain the non-responsiveness to antiplatelet therapy.

| S-EPMC7048746 | biostudies-literature

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