Neuroimaging Spectrum at Pre-, Early, and Late Symptomatic Stages of SCA17 Mice.

Spinocerebellar ataxia (SCA) is a hereditary neurodegenerative disease. We have generated SCA17 transgenic mice bearing human TBP with 109 CAG repeats under the Purkinje cell-specific L7/pcp2 promoter. These mice recapitulate the patients' phenotypes and are suitable for the study of the SCA17 pathomechanism. Magnetic resonance imaging (MRI) and immunostainings were performed to identify the neuroimaging spectrum during disease progression. The results indicate that despite an overall normal appearance at birth, postnatal brain damage takes place rapidly in SCA17. Cerebellar atrophy, fourth-ventricle enlargement, and reduced cerebellar N-acetylaspartate levels were detected at the presymptomatic stage, when the mice were juvenile. The aberrations, which included reductions in body weight; cerebral size; striatal size; and the mean, radial, and axial diffusivities of the cerebellum, became more salient as the disease progressed to the old, late-symptomatic stage. Phosphorylated H2A histone family, member X (γH2AX) immunostaining revealed that the cerebellum underwent severe cell senescence in the old stage while the striatum appeared relatively unaffected by aging. Morphometric analysis indicated that the cerebellar atrophy occurred in all subregions with aging. The data establish that the SCA17 mouse brain appears normal at birth but becomes aberrant at the presymptomatic/juvenile stage. More widespread deficits add to the pathological spectrum at the old stage. The study provides information for the expression and expansion of L7/pcp2 promoter and implies the disease progression of SCA17 patients.

Inhibition of astrocytic activity alleviates sequela in acute stages of intracerebral hemorrhage.

Neurological deterioration of intracerebral hemorrhage (ICH) mostly occurs within the first 24 hours. Together with the microglia/macrophages (MMΦ), astrocytes are important cell population responsible for many brain injuries but rarely being highlighted in acute stage of ICH. In present study, we induced rats ICH either by collagenase or autologous blood injection. Experimental groups were classified as vehicle or Ethyl-1-(4-(2,3,3-trichloroacrylamide)phenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate (Pyr3) treatment group (n = 9, each group). MRI assessments after ICH were used to evaluate the hematoma progression and blood-brain barrier (BBB) integrity. The glia cells accumulations were examined by GFAP and Iba1 immunohistochemistry, respectively. Abundant astrocytes but few MMΦ were observed in hyperacute and acute ICH. Upon suppression of astrocyte activity, ICH rats exhibited decreased size of hematoma expansion, less BBB destruction, reduced astrocyte accumulation in perihematomal regions, postponed course of hemoresolution and gain better outcomes. These finding provide evidence that activated astrocytes are crucial cell populations in hyperacute and acute ICH, and their modulation may offer opportunities for novel therapy and patient management.

The value of real-time continuous glucose monitoring in premature infants of diabetic mothers.

To determine the feasibility of using a real-time continuous glucose monitoring system (RTGMS) in intensive care units, our study focus on preterm infants with diabetic mothers owing to their high risk of blood sugar abnormalities. Thirty preterm babies (M = 15 and F = 15; ≤ 36 week gestation age) were studied from within 72 hours of delivery. These babies were admitted to the newborn intensive care and were further categorized into groups based on whether their mothers with or without diabetic mellitus. Blood sugar levels were monitored by both RTGMS and the traditional intermittent arterial line (A-Line) glucose method. Continuous glucose monitoring were well tolerated in 30 infants. There were good consistency between RTGMS and A-Line glucose concentration measurements. Of the preterm infants, 33.33% experienced abnormal glucose levels (hypoglycemia or hyperglycemia) between the checkpoint intervals of the intermittent A-Line blood sugar measurements. RTGM showed advantages with regards to reduced pain, greater comfort, the provision of real-time information, high sensitivity (94.59%) and specificity (97.87%) in discovering abnormalities of blood sugar, which are especially valuable for premature infants of diabetic mothers. RTGMS is comparable to A-line measurement for identifying fluctuations in blood glucose in premature infants. RTGMS detects more episodes of abnormal glucose concentration than intermittent A-line blood glucose measurement. High risk infants, especially premature infants with diabetic mothers, should receive more intensive blood sugar level checks by using continuous RTGMS.

Asthma and early herniated intervertebral disc disease.

BACKGROUND: The etiology of herniated intervertebral disc (HIVD) disease in children and adolescents is multifactorial and not merely related to disc degeneration. Therefore, in the present study, we investigated the relationship between young asthma patients and the risk of early HIVD disease in a population under 30 years of age. METHODS: Data from the National Health Insurance Research Database (NHIRD) of Taiwan were used to conduct a retrospective longitudinal cohort study. The study cohort comprised 23,470 patients with asthma (asthma group) and 23,470 patients without asthma (non-asthma group), who were selected through frequency matching on the basis of sex, age, and the index year. The study patients were followed until HIVD disease occurrence, withdrawal from the National Health Insurance program, or 31 December 2013. Cox proportional hazards regression analysis was conducted to assess the risk of HIVD disease in the asthma group after adjustment for sex, age, and comorbidities. RESULTS: After adjustment for sex, age, and comorbidities, the asthma group had a 1.69-fold (95% confidence interval [CI] = 1.29-2.23) higher risk of HIVD disease than did the non-asthma group. In addition, the asthma group had a higher risk of cervical and lumbar HIVD diseases than did the non-asthma group (adjusted hazard ratio [HR] = 2.38; 95% CI = 1.25-4.57 and adjusted HR = 1.56; 95% CI = 1.15-2.12, respectively). CONCLUSIONS: Young patients with asthma are at a significantly higher risk of early cervical or lumbar HIVD disease.

Functional assessment of glioma pathogenesis by in vivo multi-parametric magnetic resonance imaging and in vitro analyses.

Gliomas are aggressive brain tumors with poor prognosis. In this study, we report a novel approach combining both in vivo multi-parametric MRI and in vitro cell culture assessments to evaluate the pathogenic development of gliomas. Osteopontin (OPN), a pleiotropic factor, has been implicated in the formation and progression of various human cancers, including gliomas, through its functions in regulating cell proliferation, survival, angiogenesis, and migration. Using rat C6 glioma model, the combined approach successfully monitors the acquisition and decrease of cancer hallmarks. We show that knockdown of the expression of OPN reduces C6 cell proliferation, survival, viability and clonogenicity in vitro, and reduces tumor burden and prolongs animal survival in syngeneic rats. OPN depletion is associated with reduced tumor growth, decreased angiogenesis, and an increase of tumor-associated metabolites, as revealed by T2-weighted images, diffusion-weighted images, K(trans) maps, and 1H-MRS, respectively. These strategies allow us to define an important role of OPN in conferring cancer hallmarks, which can be further applied to assess the functional roles of other candidate genes in glioma. In particular, the non-invasive multi-parametric MRI measurement of cancer hallmarks related to proliferation, angiogenesis and altered metabolism may serve as a useful tool for diagnosis and for patient management.

Promoted Growth of Brain Tumor by the Transplantation of Neural Stem/Progenitor Cells Facilitated by CXCL12.

The targeted migration of neural stem/progenitor cells (NSPCs) is a prerequisite for the use of stem cell therapy in the treatment of pathologies. This migration is regulated mainly by C-X-C motif chemokine 12 (CXCL12). Therefore, promotion of the migratory responses of grafted cells by upregulating CXCL12 signaling has been proposed as a strategy for improving the efficacy of such cell therapies. However, the effects of this strategy on brain tumors have not yet been examined in vivo. The aim of the present study was thus to elucidate the effects of grafted rat green fluorescent protein (GFP)-labeled NSPCs (GFP-NSPCs) with CXCL12 enhancement on a model of spontaneous rat brain tumor induced by N-ethyl-N-nitrosourea. T2-weighted magnetic resonance imaging was applied to determine the changes in tumor volume and morphology over time. Postmortem histology was performed to confirm the tumor pathology, expression levels of CXCL12 and C-X-C chemokine receptor type 4, and the fate of GFP-NSPCs. The results showed that the tumor volume and hypointense areas of T2-weighted images were both significantly increased in animals treated with combined NSPC transplantation and CXCL12 induction, but not in control animals or in those with tumors that received only one of the treatments. GFP-NSPCs appear to migrate toward tumors with CXCL12 enhancement and differentiate uniquely into a neuronal lineage. These findings suggest that CXCL12 is an effective chemoattractant that facilitates exogenous NSPC migration toward brain tumors and that CXCL12 and NSPC can act synergistically to promote tumor progression with severe hemorrhage.