Susceptibility weighted MRI pinpoints spontaneous intracerebral hemorrhage in stroke-prone spontaneously hypertensive rats.

Purpose: To find magnetic resonance imaging (MRI) precursors of spontaneous intracerebral hemorrhage in stroke-prone spontaneously hypertensive rats (SHRSP).

Method: SHRSP rats were used with both a low/high salt (n = 18 or 11) Japanese diet and salty drinking water to generate spontaneous intracerebral hemorrhage (ICH). Various MRI sequences, and in particular, susceptibility weighted imaging (SWI), were used and combined with a gadolinium (Gd) contrast agent or oxygen gas to identify the rupture of the blood brain barrier (BBB) and the temporal ICH.

Quantification of human plasma metalloproteins in multiple sclerosis, ischemic stroke and healthy controls reveals an association of haptoglobin-hemoglobin complexes with age.

Advanced analytical methods play an important role in quantifying serum disease biomarkers. The problem of separating thousands of proteins can be reduced by analyzing for a 'sub-proteome', such as the 'metalloproteome', defined as all proteins that contain bound metals. We employed size exclusion chromatography (SEC) coupled to an inductively coupled plasma atomic emission spectrometer (ICP-AES) to analyze plasma from multiple sclerosis (MS) participants (n = 21), acute ischemic stroke (AIS) participants (n = 17) and healthy controls (n = 21) for Fe, Cu and Zn-metalloproteins.

PBT2 acts through a different mechanism of action than other 8-hydroxyquinolines: an X-ray fluorescence imaging study.

8-Hydroxyquinolines (8HQs) comprise a family of metal-binding compounds that have been used or tested for use in numerous medicinal applications, including as treatments for bacterial infection, Alzheimer's disease, and cancer. Two key 8HQs, CQ (5-chloro-7-iodo-8-hydroxyquinoline) and PBT2 (2-(dimethylamino)methyl-5,7-dichloro-8-hydroxyquinoline), have drawn considerable interest and have been the focus of many studies investigating their in vivo properties. These drugs have been described as copper and zinc ionophores because they do not cause metal depletion, as would be expected for a chelation mechanism, but rather cellular accumulation of these ions.

Prolonged Blood-Brain Barrier Injury Occurs After Experimental Intracerebral Hemorrhage and Is Not Acutely Associated with Additional Bleeding.

Intracerebral hemorrhage (ICH) causes blood-brain barrier (BBB) damage along with altered element levels in the brain. BBB permeability was quantified at 3, 7, and 14 days with Evans Blue dye after collagenase-induced ICH in rat. At peak permeability (day 3), a gadolinium (Gd)-based contrast agent was injected to further characterize BBB disruption, and X-ray fluorescence imaging (XFI) was used to map Gd, Fe, Cl, and other elements.

Protein-Energy Malnutrition Exacerbates Stroke-Induced Forelimb Abnormalities and Dampens Neuroinflammation.

Protein-energy malnutrition (PEM) pre-existing at stroke onset is believed to worsen functional outcome, yet the underlying mechanisms are not fully understood. Since brain inflammation is an important modulator of neurological recovery after stroke, we explored the impact of PEM on neuroinflammation in the acute period in relation to stroke-initiated sensori-motor abnormalities. Adult rats were fed a low-protein (LP) or normal protein (NP) diet for 28 days before inducing photothrombotic stroke (St) in the forelimb region of the motor cortex or sham surgery; the diets continued for 3 days after the stroke.

Examining potential side effects of therapeutic hypothermia in experimental intracerebral hemorrhage.

Studies treating intracerebral hemorrhage (ICH) with therapeutic hypothermia (TH) have shown inconsistent benefits. We hypothesized that TH's anti-inflammatory effects may be responsible as inflammatory cells are essential for removing degrading erythrocytes. Here, we subjected rats to a collagenase-induced striatal ICH followed by whole-body TH (∼33℃ for 11-72 h) or normothermia.

Rehabilitation Augments Hematoma Clearance and Attenuates Oxidative Injury and Ion Dyshomeostasis After Brain Hemorrhage.

Background And Purpose: We assessed the elemental and biochemical effects of rehabilitation after intracerebral hemorrhage, with emphasis on iron-mediated oxidative stress, using a novel multimodal biospectroscopic imaging approach.

Methods: Collagenase-induced striatal hemorrhage was produced in rats that were randomized to enriched rehabilitation or control intervention starting on day 7. Animals were euthanized on day 14 or 21, a period of ongoing cell death.

A novel multi-modal platform to image molecular and elemental alterations in ischemic stroke.

Stroke is a major global health problem, with the prevalence and economic burden predicted to increase due to aging populations in western society. Following stroke, numerous biochemical alterations occur and damage can spread to nearby tissue. This zone of "at risk" tissue is termed the peri-infarct zone (PIZ).

Novel bio-spectroscopic imaging reveals disturbed protein homeostasis and thiol redox with protein aggregation prior to hippocampal CA1 pyramidal neuron death induced by global brain ischemia in the rat.

Global brain ischemia resulting from cardiac arrest and cardiac surgery can lead to permanent brain damage and mental impairment. A clinical hallmark of global brain ischemia is delayed neurodegeneration, particularly within the CA1 subsector of the hippocampus. Unfortunately, the biochemical mechanisms have not been fully elucidated, hindering optimization of current therapies (i.

Design of a mouse restraint for synchrotron-based computed tomography imaging.

High-resolution computed tomography (CT) imaging of a live animal within a lead-lined synchrotron light hutch presents several unique challenges. In order to confirm that the animal is under a stable plane of anaesthesia, several physiological parameters (e.g.

A new method to image heme-Fe, total Fe, and aggregated protein levels after intracerebral hemorrhage.

An intracerebral hemorrhage (ICH) is a devastating stroke that results in high mortality and significant disability in survivors. Unfortunately, the underlying mechanisms of this injury are not yet fully understood. After the primary (mechanical) trauma, secondary degenerative events contribute to ongoing cell death in the peri-hematoma region.

In situ biospectroscopic investigation of rapid ischemic and postmortem induced biochemical alterations in the rat brain.

Rapid advances in imaging technologies have pushed novel spectroscopic modalities such as Fourier transform infrared spectroscopy (FTIR) and X-ray absorption spectroscopy (XAS) at the sulfur K-edge to the forefront of direct in situ investigation of brain biochemistry. However, few studies have examined the extent to which sample preparation artifacts confound results. Previous investigations using traditional analyses, such as tissue dissection, homogenization, and biochemical assay, conducted extensive research to identify biochemical alterations that occur ex vivo during sample preparation.

The solution structure of the copper clioquinol complex.

Clioquinol (5-chloro-7-iodo-8-hydroxyquinoline) recently has shown promising results in the treatment of Alzheimer's disease and in cancer therapy, both of which also are thought to be due to clioquinol's ability as a lipophilic copper chelator. Previously, clioquinol was used as an anti-fungal and anti-protozoal drug that was responsible for an epidemic of subacute myelo-optic neuropathy (SMON) in Japan during the 1960s, probably a myeloneuropathy arising from a clioquinol-induced copper deficiency. Previous X-ray absorption spectroscopy of solutions of copper chelates of clioquinol suggested unusual coordination chemistry.

Subcellular biochemical investigation of purkinje neurons using synchrotron radiation fourier transform infrared spectroscopic imaging with a focal plane array detector.

Coupling Fourier transform infrared spectroscopy with focal plane array detectors at synchrotron radiation sources (SR-FTIR-FPA) has provided a rapid method to simultaneously image numerous biochemical markers in situ at diffraction limited resolution. Since cells and nuclei are well resolved at this spatial resolution, a direct comparison can be made between FTIR functional group images and the histology of the same section. To allow histological analysis of the same section analyzed with infrared imaging, unfixed air-dried tissue sections are typically fixed (after infrared spectroscopic analysis is completed) via immersion fixation.

Measuring iron in the brain using quantitative susceptibility mapping and X-ray fluorescence imaging.

Measuring iron content in the brain has important implications for a number of neurodegenerative diseases. Quantitative susceptibility mapping (QSM), derived from magnetic resonance images, has been used to measure total iron content in vivo and in post mortem brain. In this paper, we show how magnetic susceptibility from QSM correlates with total iron content measured by X-ray fluorescence (XRF) imaging and by inductively coupled plasma mass spectrometry (ICPMS).

X-ray absorption spectroscopy at the sulfur K-edge: a new tool to investigate the biochemical mechanisms of neurodegeneration.

Sulfur containing molecules such as thiols, disulfides, sulfoxides, sulfonic acids, and sulfates may contribute to neurodegenerative processes. However, previous study in this field has been limited by the lack of in situ analytical techniques. This limitation may now be largely overcome following the development of synchrotron radiation X-ray absorption spectroscopy at the sulfur K-edge, which has been validated as a novel tool to investigate and image the speciation of sulfur in situ.

Imaging of stroke: a comparison between X-ray fluorescence and magnetic resonance imaging methods.

A dual imaging approach, combining magnetic resonance imaging to localize lesions and synchrotron rapid scanning X-ray fluorescence (XRF) mapping to localize and quantify calcium, iron and zinc was used to examine one case of recent stroke with hemorrhage and two cases of ischemia 3 and 7 years before death with the latter showing superficial necrosis. In hemorrhagic lesions, more Fe is found accompanied with less Zn. In chronic ischemic lesions, Fe, Zn and Ca are lower indicating that these elements are removed as the normal tissue dies and scar tissue forms.

Prolonged therapeutic hypothermia does not adversely impact neuroplasticity after global ischemia in rats.

Hypothermia improves clinical outcome after cardiac arrest in adults. Animal data show that a day or more of cooling optimally reduces edema and tissue injury after cerebral ischemia, especially after longer intervention delays. Lengthy treatments, however, may inhibit repair processes (e.

Ferric iron chelation lowers brain iron levels after intracerebral hemorrhage in rats but does not improve outcome.

Iron-mediated free radical damage contributes to secondary damage after intracerebral hemorrhage (ICH). Iron is released from heme after hemoglobin breakdown and accumulates in the parenchyma over days and then persists in the brain for months (e.g.

A median-Gaussian filtering framework for Moiré pattern noise removal from X-ray microscopy image.

Moiré pattern noise in Scanning Transmission X-ray Microscopy (STXM) imaging introduces significant errors in qualitative and quantitative image analysis. Due to the complex origin of the noise, it is difficult to avoid Moiré pattern noise during the image data acquisition stage. In this paper, we introduce a post-processing method for filtering Moiré pattern noise from STXM images.

Innate immune responses of Drosophila melanogaster are altered by spaceflight.

Alterations and impairment of immune responses in humans present a health risk for space exploration missions. The molecular mechanisms underpinning innate immune defense can be confounded by the complexity of the acquired immune system of humans. Drosophila (fruit fly) innate immunity is simpler, and shares many similarities with human innate immunity at the level of molecular and genetic pathways.

Mapping brain metals to evaluate therapies for neurodegenerative disease.

The brain is rich in metals and has a high metabolic rate, making it acutely vulnerable to the toxic effects of endogenously produced free radicals. The abundant metals, iron and copper, transfer single electrons as they cycle between their reduced (Fe(2+) , Cu(1+) ) and oxidized (Fe(3+) , Cu(2+) ) states making them powerful catalysts of reactive oxygen species (ROS) production. Even redox inert zinc, if present in excess, can trigger ROS production indirectly by altering mitochondrial function.

Brain iron detected by SWI high pass filtered phase calibrated with synchrotron X-ray fluorescence.

Purpose: To test the ability of susceptibility weighted images (SWI) and high pass filtered phase images to localize and quantify brain iron.

Materials And Methods: Magnetic resonance (MR) images of human cadaver brain hemispheres were collected using a gradient echo based SWI sequence at 1.5T.

Synchrotron X-ray fluorescence reveals abnormal metal distributions in brain and spinal cord in spinocerebellar ataxia: a case report.

For the first time, synchrotron rapid-scanning X-ray fluorescence (RS-XRF) was used to simultaneously localize and quantify iron, copper, and zinc in spinal cord and brain in a case of spinocerebellar ataxia (SCA). In the normal medulla, a previously undescribed copper enrichment was seen associated with spinocerebellar fibers and amiculum olivae. This region was virtually devoid of all metals in the SCA case.

Iron, copper, and zinc distribution of the cerebellum.

Synchrotron rapid-scanning X-ray fluorescence (RS-XRF) is employed for the first time to simultaneously map iron, copper, and zinc in the normal cerebellum. The cerebellum is a major repository of metals that are essential to normal function. Therefore, mapping the normal metal distribution is an important first step towards understanding how multiple metals may induce oxidative damage, protein aggregation, and neurotoxicity leading to cerebellar degeneration in a wide range of diseases.