[Show abstract][Hide abstract] ABSTRACT: Convincing epidemiological data suggest an inverse association between cancer and neurodegeneration, including Alzheimer's disease (AD). Since both AD and cancer are characterized by abnormal, but opposing cellular behavior, i.e., increased cell death in AD while excessive cell growth occurs in cancer, this motivates us to initiate the study into unraveling the shared genes and cell signaling pathways linking AD and glioblastoma multiform (GBM). In this study, a comprehensive bioinformatics analysis on clinical microarray datasets of 1,091 GBM and 524 AD cohorts was performed. Significant genes and pathways were identified from the bioinformatics analyses - in particular ERK/MAPK signaling, up-regulated in GBM and Angiopoietin Signaling pathway, reciprocally up-regulated in AD - connecting GBM and AD (P < 0.001), were investigated in details for their roles in GBM growth in an AD environment. Our results showed that suppression of GBM growth in an AD background was mediated by the ERK-AKT-p21-cell cycle pathway and anti-angiogenesis pathway.
[Show abstract][Hide abstract] ABSTRACT: Decreased cerebral blood flow causes brain ischemia and plays an important role in the pathophysiology of many neurodegenerative diseases, including Alzheimer's disease and vascular dementia. In this study, we photomodulated astrocytes in the live animal by a combination of two-photon calcium uncaging in the astrocyte endfoot and in vivo imaging of neurovasculature and astrocytes by intravital two-photon microscopy after labeling with cell type specific fluorescent dyes. Our study demonstrates that photomodulation at the endfoot of a single astrocyte led to a 25% increase in the diameter of a neighboring arteriole, which is a crucial factor regulating cerebral microcirculation in downstream capillaries. Two-photon uncaging in the astrocyte soma or endfoot near veins does not show the same effect on microcirculation. These experimental results suggest that infrared photomodulation on astrocyte endfeet may be a strategy to increase cerebral local microcirculation and thus prevent brain ischemia.
Journal of Biomedical Optics 12/2013; 18(12):126012. · 2.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Thrombus and secondary thrombosis plays a key role in stroke. Recent molecular imaging provides in vivo imaging of activated factor XIII (FXIIIa), an important mediator of thrombosis or fibrinolytic resistance. The present study was to investigate the fibrin deposition in a thromboembolic stroke mice model by FXIIIa-targeted near-infrared fluorescence (NIRF) imaging.
The experimental protocol was approved by our institutional animal use committee. Seventy-six C57B/6J mice were subjected to thromboembolic middle cerebral artery occlusion or sham operation. Mice were either intravenously injected with the FXIIIa-targeted probe or control probe. In vivo and ex vivo NIRF imaging were performed thereafter. Probe distribution was assessed with fluorescence microscopy by spectral imaging and quantification system. MR scans were performed to measure lesion volumes in vivo, which were correlated with histology after animal euthanasia.
In vivo significant higher fluorescence intensity over the ischemia-affected hemisphere, compared to the contralateral side, was detected in mice that received FXIIIa-targeted probe, but not in the controlled mice. Significantly NIRF signals showed time-dependent processes from 8 to 96 hours after injection of FXIIIa-targeted probes. Ex vivo NIRF image showed an intense fluorescence within the ischemic territory only in mice injected with FXIIIa-targeted probe. The fluorescence microscopy demonstrated distribution of FXIIIa-targeted probe in the ischemic region and nearby micro-vessels, and FXIIIa-targeted probe signals showed good overlap with immune-fluorescent fibrin staining images. There was a significant correlation between total targeted signal from in vivo or ex vivo NIRF images and lesion volume.
Non-invasive detection of fibrin deposition in ischemic mouse brain using NIRF imaging is feasible and this technique may provide an in vivo experimental tool in studying the role of fibrin in stroke.
PLoS ONE 01/2012; 7(1):e30262. · 3.53 Impact Factor