The failure of the remyelination processes in multiple sclerosis contributes to the formation of chronic demyelinated plaques that lead to severe neurological deficits. Long-term cuprizone treatment of C57BL/6 mice resulted in pronounced white matter pathology characterized by oligodendrocyte depletion, irreversible demyelination and persistent functional deficits after cuprizone withdrawal. The use of a combination of in vivo diffusion tensor magnetic resonance imaging (DT-MRI) and histological analyses allowed for an accurate longitudinal assessment of demyelination. Injection of triiodothyronine (T3) hormone over a 3 week interval after cuprizone withdrawal progressively restored the normal DT-MRI phenotype accompanied by an improvement of clinical signs and remyelination. The effects of T3 were not restricted to the later stages of remyelination but increased the expression of sonic hedgehog and the numbers of Olig2+ and PSA-NCAM+ precursors and proliferative cells. Our findings establish a role for T3...

Within both the machine learning and cognitive neuroscience communities, there has been recent interest in estimating brain states using functional magnetic resonance imaging (fMRI) data. Research groups have referred to this type of analysis as multi-v...

The ability to identify embryonic neural stem cells after therapeutic transplantation is crucial. In particular, there is a need for a non-invasive, longitudinal method of in vivo tracking of such cellular therapies. Embryonic neural stem cells derived from E14 rat spinal cord tissue were co-incubated with encapsulated microspheres (Bangs Laboratories). Each microsphere is 0.96 µm and consists of iron oxide crystals and a fluorescein analogue entrapped in a polymer matrix. Electron microscopy confirmed the intracytoplasmic location of these microspheres after co-culture. Fluorescence and light microscopy confirmed a highly efficient labeling process and the healthy appearance of cells. Magnetic resonance imaging (MRI) was performed at 7.0 Tesla using a Bruker Biospin system. In vitro MRI of labeled, cultured cells demonstrated the ability to resolve individual embryonic neural stem cells. In vivo studies used a spinal cord overhemisection lesion at C4. Labeled embryonic neural stem cells were transplanted ...

With the development of high-resolution anatomical magnetic resonance imaging (MRI) and automated statistical analysis techniques, brain morphometry has emerged as a dynamic field in neuroscience. A variety of techniques are now used to assess gray and white matter characteristics, such as thickness

Experimental autoimmune encephalomyelitis (EAE) is a well-established model for multiple sclerosis (MS) that is characterized by spinal cord pathology progressing in a caudal to cranial direction. Currently, demyelinated lesions are visualized in mice u...

The Model Organism Development and Evaluation for Late-Onset Alzheimer’s Disease (MODEL-AD) consortium has been established to develop the next generation of Alzheimer’s disease (AD) models based on human data. As these models are developed, they are ri...

Manganese-enhanced magnetic resonance imaging (MEMRI) provides a powerful tool to study multisynaptic circuits in vivo and thereby to link information about neural structure and function within individual subjects. Making the best use of MEMRI in monkeys requires minimizing manganese-associated neurotoxicity, maintaining sensitivity to manganese-dependent signal changes and mapping transport throughout the brain without a priori anatomical hypotheses. Here, we performed intracortical injections of isotonic MnCl2, comparisons of preinjection and postinjection scans, and voxelwise statistical mapping. Isotonic MnCl2 did not cause cell death at the injection site, damage to downstream targets of manganese transport, behavioral deficits, or changes in neuronal responsiveness. We detected and mapped manganese transport throughout cortical–subcortical circuits by using voxelwise statistical comparisons of at least 10 preinjection and two postinjection scans. We were able to differentiate between focal and diffus...

The cause of the chronic nigrostriatal degeneration in Parkinson’s disease (PD) remains unknown. The ability to study ongoing degeneration in vivo over a condensed time period in an animal model offers an opportunity to study potential mechanisms and markers of PD. The purpose of this study was to determine striatal magnetic resonance imaging (MRI) and spectroscopy (MRS) changes after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment in cats. Six adult, specific-pathogen free, male cats were divided into 2 equal groups. Three control cats received saline daily (1 ml/kg SC) while 3 cats received MPTP (5 mg/kg SC) for 10 consecutive days. Pargyline, a MAO inhibitor, was given concurrently (35-50 mg/kg SC) to one MPTP cat (MPTP+PG). Baseline and post-treatment measurements included neurologic examinations, sensory evoked potentials, MRI and proton MRS studies of the basal ganglia. Striatal tissue was collected for histopathologic and neurochemical analysis. MPTP alone treated cats demonstrated bra...

Sex-specific behaviors are in part based on hormonal regulation of brain physiology. This functional magnetic resonance imaging (fMRI) study demonstrated significant differences in activation of hypothalamic-pituitary-adrenal (HPA) circuitry in adult women with attenuation during ovulation and increased activation during early follicular phase. Twelve normal premenopausal women were scanned twice during the early follicular menstrual cycle phase compared with late follicular/midcycle, using negative valence/high arousal versus neutral visual stimuli, validated by concomitant electrodermal activity (EDA). Significantly greater magnitude of blood oxygenation level-dependent signal changes were found during early follicular compared with midcycle timing in central amygdala, paraventricular and ventromedial hypothalamic nuclei, hippocampus, orbitofrontal cortex (OFC), anterior cingulate gyrus (aCING), and peripeduncular nucleus of the brainstem, a network of regions implicated in the stress response. Arousal (...

Functional magnetic resonance imaging (fMRI) has revolutionized investigations of brain functions. Increases in fMRI signals are usually correlated with neuronal activation, but diverse explanations have been proposed for negative fMRI responses, including decreases in neuronal activity, the vascular-steal effect, and large increases in oxygen consumption. These possible scenarios, although encompassing a wide range of potential neurovascular responses, cannot yet be used to interpret certain types of negative fMRI signals. Recent studies have found that intravenous injection of dopamine D2 receptor (D2DR) agonist reduced the hemodynamic responses in the caudate–putamen (CPu); however, whether endogenous dopaminergic neurotransmission contributes to fMRI signals remains obscure. Since it has been suggested that the D2DR is involved in pain modulation, and the CPu shows equivocal fMRI signals during noxious stimulation, the present study established an animal model based on graded electrical stimulation to ...