Blood brain barrie stroke

BACKGROUND AND PURPOSE: We investigated changes in oxidative damage after ischemic stroke using multiple biomarkers. METHODS: Serial blood and urine samples of ischemic stroke subjects and age-matched control subjects were assayed for F₂-isoprostanes, hydroxyeicosatetraenoic acid products, F₄-neuroprostanes, 24-hydroxycholesterol, allantoin, and urate. RESULTS: Sixty-six stroke subjects (mean age, 65 years; median National Institutes of Health Stroke Scale 17) and 132 control subjects were recruited...

Magnetic resonance imaging (MRI) with oxygen challenge (T(2)(*) OC) uses oxygen as a metabolic biotracer to define penumbral tissue based on CMRO(2) and oxygen extraction fraction. Penumbra displays a greater T(2)(*) signal change during OC than surrounding tissue. Since timely restoration of cerebral blood flow (CBF) should salvage penumbra, T(2)(*) OC was tested by examining the consequences of reperfusion on T(2)(*) OC-defined penumbra. Transient ischemia (109 ± 20 minutes) was induced in male Sprague-Dawley rats (n=8)...

BACKGROUND: Raised intracranial pressure (ICP) following SAH predicts poor outcome and is due to hemorrhage volume and possibly, brain edema, hydrocephalus and increased volume of circulating intracranial blood. Interventions that reduce edema may therefore reduce ICP and improve outcome. The neuropeptide substance P (SP) mediates vasogenic edema formation in animal models of ischemic stroke, intracerebral hemorrhage and brain trauma, and may contribute to development of increased ICP...

Lipoic acid (LA) is a known antioxidant currently used as a therapy in patients with vascular and metabolic disorders. We tested the hypothesis that lipoic acid is protective against the cell death observed following stroke. Lipoic acid was administered 30minutes prior to, or immediately following removal of sutures used to occlude the middle cerebral artery (MCA) in male Sprague-Dawley rats. Following removal of the sutures, the MCA territory was allowed to undergo 5.5hrs of reperfusion. This ischemia/reperfusion (I/R) resulted in a focal infarct restricted to the prefrontal cortex (24±3mm(3))...

OBJECTIVE: Poststroke hyperglycemia is common and is associated with increased risk of death and dependence, but appropriate management remains uncertain. Glucose potassium insulin (GKI) infusion did not benefit patients with moderate poststroke hyperglycemia in a recent trial. Using magnetic resonance imaging (MRI), previous studies identified a relationship between recruitment of ischemic tissue to the final infarct and hyperglycemia, possibly mediated by brain lactic acidosis. METHODS: We undertook a randomized, placebo-controlled trial of GKI infusion in patients with blood glucose >126mg/dl (7mmol/l) within 24 hours of ischemic stroke...

BACKGROUND: Aldosterone antagonism has been studied in patients with advanced heart failure (HF) and also in patients with post-myocardial infarction and left ventricular (LV) dysfunction with HF symptoms. Few data are available on effects of aldosterone antagonism in patients with mild-to-moderate HF. METHODS AND RESULTS: In a multicenter, randomized, double-blind, placebo-controlled study in patients with mild-to-moderate HF and LV systolic dysfunction, patients with New York Heart Association class II/III HF and LV ejection fraction (EF) < or =35% were randomly assigned to receive eplerenone 50 mg/d versus placebo in addition to contemporary background therapy...

We sought to clarify the significance of cardiac dysfunction and to assess its relationship with elevated biomarkers by using cardiovascular magnetic resonance imaging in healthy, middle-aged subjects immediately after they ran 26.2 miles. Cardiac dysfunction and elevated blood markers of myocardial injury have been reported after prolonged strenuous exercise. From 425 volunteers, 13 women and 12 men were randomly selected, provided medical and training history, and underwent baseline cardiopulmonary exercise testing to exhaustion...

Obesity is an independent risk factor for stroke and is associated with poorer outcome after stroke. We investigated whether this poorer outcome is related to brain microvascular disruption. Focal cerebral ischaemia was induced in lean or obese (ob/ob) mice by transient middle cerebral artery occlusion. The incidence of haemorrhagic transformation and the volume of ischaemic brain damage were significantly greater in obese mice. Blood-brain barrier permeability and brain microvascular MMP-9 expression were also markedly increased in obese mice...

Astaxanthin (ATX) is a dietary carotenoid of crustaceans and fish that contributes to their coloration. Dietary ATX is important for development and survival of salmonids and crustaceans and has been shown to reduce cardiac ischemic injury in rodents. The purpose of this study was to examine whether ATX can protect against ischemic injury in the mammalian brain. Adult rats were injected intracerebroventricularly with ATX or vehicle prior to a 60-min middle cerebral artery occlusion (MCAo). ATX was present in the infarction area at 70-75 min after onset of MCAo...

Glucagon-like peptide-1 (GLP-1) is an endogenous insulinotropic peptide secreted from the gastrointestinal tract in response to food intake. It enhances pancreatic islet beta-cell proliferation and glucose-dependent insulin secretion, and lowers blood glucose and food intake in patients with type 2 diabetes mellitus (T2DM). A long-acting GLP-1 receptor (GLP-1R) agonist, exendin-4 (Ex-4), is the first of this new class of antihyperglycemia drugs approved to treat T2DM. GLP-1Rs are coupled to the cAMP second messenger pathway and, along with pancreatic cells, are expressed within the nervous system of rodents and humans, where receptor activation elicits neurotrophic actions...

Systemic inflammatory events, such as infection, increase the risk of stroke and are associated with worse outcome, but the mediators of this clinically important effect are unknown. Our aim here was to elucidate mechanisms contributing to the detrimental effects of systemic inflammation on mild ischemic brain injury in mice. Systemic inflammation was induced in mice by peripheral interleukin-1beta (IL-1beta) challenge and focal cerebral ischemia by transient middle cerebral artery occlusion (MCAo). Systemic inflammation caused an alteration in the kinetics of blood-brain barrier (BBB) disruption through conversion of a transient to a sustained disruption of the tight junction protein, claudin-5, and also markedly exacerbated disruption to the cerebrovascular basal lamina protein, collagen-IV...

BACKGROUND: Strategies to preserve renal function and enhance diuretic responsiveness during therapy for heart failure (HF) are needed. We hypothesized that brain natriuretic peptide (nesiritide) added to standard HF therapy would preserve renal function and enhance diuretic responsiveness. METHODS: Patients with HF with underlying renal dysfunction who were admitted with volume overload were randomized to standard therapy with nesiritide (2 mug/kg bolus; 0.01 mug/kg/min for 48 hours) or without nesiritide...

BACKGROUND: There are no randomized, controlled trial data to support the benefit of beta-blockers in patients with asymptomatic left ventricular systolic dysfunction. We investigated whether beta-blocker therapy ameliorates left ventricular remodeling in asymptomatic patients with left ventricular systolic dysfunction. METHOD AND RESULTS: Patients with left ventricular ejection fraction <40%, mild left ventricular dilation, and no symptoms of heart failure (New York Heart Association class I) were randomly assigned to receive extended-release metoprolol succinate (Toprol-XL, AstraZeneca) 200 mg or 50 mg or placebo for 12 months...

BACKGROUND: Mechanisms purported to contribute to the pathophysiology of heart failure with normal ejection fraction (HFnlEF) include diastolic dysfunction, vascular and left ventricular systolic stiffening, and volume expansion. We characterized left ventricular volume, effective arterial elastance, left ventricular end-systolic elastance, and left ventricular diastolic elastance and relaxation noninvasively in consecutive HFnlEF patients and appropriate controls in the community. METHODS AND RESULTS: Olmsted County (Minn) residents without cardiovascular disease (n=617), with hypertension but no heart failure (n=719), or with HFnlEF (n=244) were prospectively enrolled...

BACKGROUND: Poor performance by physicians-in-training and interobserver variability between physicians have diminished clinicians' confidence in the value of the third heart sound (S3). METHODS: To determine whether auscultation of a clinically useful S3 improves with advancing levels of experience, we performed a prospective, blinded, observational study of 100 patients undergoing left-sided heart catheterization. Patients underwent blinded auscultation by 4 physicians (each from 1 of 4 different levels of experience), phonocardiography, measurement of blood B-type natriuretic peptide levels, echocardiography for measurement of left ventricular ejection fraction, and cardiac catheterization for measurement of left ventricular end-diastolic pressure...

Rodent models of focal cerebral ischaemia are critical for understanding pathophysiological concepts in human stroke. The availability of genetically modified mice has prompted the adaptation of the intraluminal filament occlusion model of focal ischaemia for use in mice. In the present study, we investigated the effects of increasing duration of intraluminal occlusion on the extent and distribution of ischaemic pathology and local cerebral blood flow (LCBF) in C57Bl/6J mice, the most common background mouse strain...

BACKGROUND AND PURPOSE: We and others have previously reported that bone morphogenetic protein-7 (BMP-7), given before middle cerebral artery occlusion (MCAO), reduces ischemic injury in brain. Recent studies have indicated that receptors for BMP are upregulated after brain ischemia. It is possible that this upregulation may facilitate endogenous neurorepair in the ischemic brain. The purpose of this study was to determine the neuroregenerative effects of BMP-7 given parenterally after ischemia/reperfusion injury...

Cyclosporine-A (CsA) is neuroprotective in animal models of Parkinson's disease (PD), Huntington's disease and stroke. Because CsA does not easily cross the blood-brain barrier (BBB), high doses (i.e. >10 mg/kg in rats) and chronic administration may be necessary to produce beneficial effects. However, immunosuppressant side effects (including nephrotoxicity and hepatotoxicity) are associated with such CsA dosing regimens. The bradykinin B2 receptor agonist, Cereport (labradimil and formerly called RMP-7), transiently increases the permeability of the BBB to facilitate delivery of drugs to the CNS...

Mild hyperhomocysteinemia is a risk factor for atherosclerotic vascular disease. Homozygosity for the C677T mutation in the gene for 5,10-methylenetetrahydrofolate reductase (MTHFR) is frequently associated with hyperhomocysteinemia, particularly in individuals with low levels of serum folate, and has been directly associated with cardiovascular disease in certain populations. The purpose of this study was to establish whether the C677T mutation, which causes thermolabile MTHFR, is a risk factor for ischemic stroke in the Irish population...