Simulation, Implementation and Measurement of Defined Sound Fields for Blood-Brain Barrier Opening in Rats.

The blood-brain barrier (BBB) is the most important obstacle to delivery of therapeutics to the central nervous system. Low-intensity pulsed focused ultrasound (FUS) in combination with microbubbles applied under magnetic resonance imaging (MRI) control provides a non-invasive and safe technique for BBB opening (BBBo). In rodent models, however, settings and application protocols differ significantly.

Intravenous treatment with human recombinant ApoA-I Milano reduces beta amyloid cerebral deposition in the APP23-transgenic mouse model of Alzheimer's disease.

Beyond the crucial role of apolipoprotein A-I (ApoA-I) on peripheral cholesterol metabolism, this apolipoprotein has also been implicated in beta amyloid (Aβ)-related neuropathologies. ApoA-I-Milano (M) is a mutated variant, which showed increased vasoprotective properties compared to ApoA-I-wild type in models of atherosclerosis and cardiovascular damage. We speculated that ApoA-I-M may also protect Aβ-affected vasculature and reverse some of the pathological features associated with Alzheimer's disease (AD).

The effect of adipose tissue-derived stem cells in a middle cerebral artery occlusion stroke model depends on their engraftment rate.

Background: In the field of experimental stem cell therapy, intra-arterial (IA) delivery yields the best results concerning, for example, migrated cell number at the targeted site. However, IA application also appears to be associated with increased mortality rates and infarction. Since many rodent studies systemically apply 1 × 10 cells, this could also be a consequence of engrafted cell number.

Development of Cerebral Microbleeds in the APP23-Transgenic Mouse Model of Cerebral Amyloid Angiopathy-A 9.4 Tesla MRI Study.

Background: Cerebral amyloid angiopathy (CAA) is characterized by extracellular deposition of amyloid β (Aβ) around cerebral arteries and capillaries and leads to an increased risk for vascular dementia, spontaneous lobar hemorrhage, convexal subarachnoid hemorrhage, and transient focal neurological episodes, which might be an indicator of imminent spontaneous intracerebral hemorrhage. In CAA cerebral microbleeds (cMBs) with a cortical/juxtacortical distribution are frequently observed in standard magnetic resonance imaging (MRI). In vivo MRI of transgenic mouse models of CAA may serve as a useful tool to investigate translational aspects of the disease.

Efficacy of Alteplase in a Mouse Model of Acute Ischemic Stroke: A Retrospective Pooled Analysis.

Background And Purpose: The debate over the fact that experimental drugs proposed for the treatment of stroke fail in the translation to the clinical situation has attracted considerable attention in the literature. In this context, we present a retrospective pooled analysis of a large data set from preclinical studies, to examine the effects of early versus late administration of intravenous recombinant tissue-type plasminogen activator.

Methods: We collected data from 26 individual studies from 9 international centers (13 researchers; 716 animals) that compared recombinant tissue-type plasminogen activator with controls, in a unique mouse model of thromboembolic stroke induced by an in situ injection of thrombin into the middle cerebral artery.

Statin Therapy and the Development of Cerebral Amyloid Angiopathy--A Rodent in Vivo Approach.

Background: Cerebral amyloid angiopathy (CAA) is characterized by vascular deposition of amyloid β (Aβ) with a higher incidence of cerebral microbleeds (cMBs) and spontaneous hemorrhage. Since statins are known for their benefit in vascular disease we tested for the effect on CAA.

Methods: APP23-transgenic mice received atorvastatin-supplemented food starting at the age of eight months (n = 13), 12 months (n = 7), and 16 months (n = 6), respectively.

Effect of simvastatin on MMPs and TIMPs in human brain endothelial cells and experimental stroke.

Clinical studies demonstrated favorable effects of statins in stroke beyond lipid-lowering effects. In acute stroke, the disruption of the blood-brain barrier (BBB) is mediated by matrix metalloproteinases (MMPs). A modified MMP metabolism may account for the beneficial effects of statins.

Thrombolysis in experimental cerebral amyloid angiopathy and the risk of secondary intracerebral hemorrhage.

Background And Purpose: Intracerebral hemorrhage (ICH) is the most adverse event of thrombolysis in ischemic stroke. Cerebral amyloid angiopathy increases the risk for spontaneous lobar ICH. Although thrombolysis may be performed in cerebral amyloid angiopathy-affected patients, there is still little knowledge available on the risk for secondary ICH.

Chlorine and sodium chemical shift imaging during acute stroke in a rat model at 9.4 Tesla.

Object: A triple-resonant coil setup with an (1)H linear resonator and a double-tuned (23)Na/(35)Cl surface coil was used to study the evolution of T 2 (*) and M 0 for (35)Cl and (23)Na in a rat stroke model during the acute phase at 9.4 Tesla.

Materials And Methods: In vivo measurements were performed 1.

Temporal profile of matrix metalloproteinases and their inhibitors in a human endothelial cell culture model of cerebral ischemia.

Background: Matrix metalloproteinases (MMPs) are key players in proteolytic blood-brain barrier (BBB) disruption during ischemic stroke, leading to vascular edema, hemorrhagic transformation and infiltration by leukocytes. Their effect is dampened by the endogenous tissue inhibitors of metalloproteinases (TIMPs). The respective cellular source of specific MMPs and TIMPs during BBB breakdown is still under investigation.

Thromboembolic stroke in C57BL/6 mice monitored by 9.4 T MRI using a 1H cryo probe.

Background: A new thromboembolic animal model showed beneficial effects of t-PA with an infarct volume reduction of 36.8% in swiss mice. Because knock-out animal experiments for stroke frequently used C57BL76 mice we evaluated t-PA effects in this mouse strain and measured infarct volume and vascular recanalisation in-vivo by using high-field 9.

Chemical shift sodium imaging in a mouse model of thromboembolic stroke at 9.4 T.

Purpose: To estimate changes in the (23)Na density and in the (23)Na relaxation time T(2) * in the anatomically small murine brain after stroke.

Materials And Methods: Three-dimensional acquisition weighted chemical shift imaging at a resolution of 0.6 × 0.

Inducible response required for repair of low-dose radiation damage in human fibroblasts.

Ionizing radiation (IR) induces a variety of DNA lesions among which DNA double-strand breaks (DSBs) are the biologically most significant. It is currently unclear if DSB repair is equally efficient after low and high doses. Here, we use gamma-H2AX, phospho-ATM (pATM), and 53BP1 foci analysis to monitor DSB repair.

Reduction of X-ray induced DNA double-strand breaks in blood lymphocytes during coronary CT angiography using high-pitch spiral data acquisition with prospective ECG-triggering.

Objectives: Purpose of this study was to compare the effect of high-pitch spiral data acquisition with prospective electrocardiography (ECG)-triggering on the x-ray induced DNA damages to blood lymphocytes with commonly used low-pitch spiral scans.

Materials And Methods: Thirty four patients underwent coronary computed tomography angiography either using high-pitch spiral data acquisition (n = 15; dual-source computed tomography (CT) scanner, 38.4 mm collimation, 100-120 kV, 320-456 mAs/rotation, pitch value 3.

Contrast medium-enhanced radiation damage caused by CT examinations.

Purpose: To assess the effect of iodinated contrast medium (CM) on the induction and repair of DNA double-strand breaks (DSBs) in peripheral blood lymphocytes after computed tomographic (CT) examinations.

Materials And Methods: This prospective study was approved by the institutional ethics committee; written informed patient consent was obtained from 37 patients. Venous blood samples were taken from patients before and at 30 minutes, 1 hour, 2.

DNA double-strand breaks and their repair in blood lymphocytes of patients undergoing angiographic procedures.

Objectives: To adapt gamma-H2AX immunofluorescence microscopy to assessment of induction and repair of DNA double-strand breaks (DSBs) in peripheral blood lymphocytes in patients undergoing angiographic procedures.

Materials And Methods: The study was approved by the institutional ethics committee. After written informed patient consents were obtained, venous blood samples were taken from 19 patients (age 23-88 years) undergoing different angiographic procedures before, during, and after (10 minutes-24 hours) the examination.

DNA double-strand break repair of blood lymphocytes and normal tissues analysed in a preclinical mouse model: implications for radiosensitivity testing.

Purpose: Radiotherapy is an effective cancer treatment, but a few patients suffer severe radiation toxicities in neighboring normal tissues. There is increasing evidence that the variable susceptibility to radiation toxicities is caused by the individual genetic predisposition, by subtle mutations, or polymorphisms in genes involved in cellular responses to ionizing radiation. Double-strand breaks (DSB) are the most deleterious form of radiation-induced DNA damage, and DSB repair deficiencies lead to pronounced radiosensitivity.