A correlation between the abnormal cerebral glucose metabolism and the progression of Alzheimer’s disease (AD) has been found in previous studies, suggesting that glucose alterations may be used to predict the histopathological diagnosis in AD. In this study, we investigated the dynamic changes of cerebral glucose uptake in vivo using MR glucose chemical exchange saturation transfer (glucoCEST) imaging in a rat model of AD with an intracerebroventricular (i.c.v) injection of amyloid Aβ-protein (25–35), confirmed by Morris water maze and Nissl staining. In total, 6 rats in the AD group and 6 rats in the control group that were given an injection of sterile normal saline were included. At 28 days after injection, all rats performed a 7.0 T MR exanimation, including glucoCEST, diffusion tensor imaging (DTI) and hippocampus magnetic resonance spectra (MRS), to detect the possible metabolic and structural changes in the rat brain. A significantly elevated brain glucoCEST signal in the brain of AD rats was observed, and a decreased brain glucose uptake was also explored during the progression of glucose infusion compared with those in rats of the control group. In addition, there is a significant positive correlation between glucoCEST enhancement (GCE) and myo-Inosito (Ins) in the AD group and the control group (P < 0.05). A significantly reduced number of neurons in the cortex and hippocampus in AD rats combined with the significantly longer escape and a decreased number of crossings were verified at 28 days after Aβ25–35 injection by Nissl staining and Morris water maze, respectively. Our results indicated that an abnormal brain glucose mechanism in AD rats could be detected by glucoCEST imaging, suggesting a new method to explore the occurrence and progress of diabetes-related AD or dementia.

Glutamate excitoxicity plays a crucial role in the pathophysiology of traumatic brain injury (TBI) through the initiation of secondary injuries. Glutamate chemical exchange saturation transfer (GluCEST) MRI is a newly developed technique to noninvasively image glutamate in vivo with high sensitivity and spatial resolution. The aim of the present study was to use a rat model of TBI to map changes in brain glutamate distribution and explore the capability of GluCEST imaging for detecting secondary injuries. Sequential GluCEST imaging scans were performed in adult male Sprague–Dawley rats before TBI and at 1, 3, 7, and 14 days after TBI. GluCEST% increased and peaked on day 1 after TBI in the core lesion of injured cortex and peaked on day 3 in the ipsilateral hippocampus, as compared to baseline and controls. GluCEST% gradually declined to baseline by day 14 after TBI. A negative correlation between the GluCEST% of the ipsilateral hippocampus on day 3 and the time in the correct quadrant was observed in injured rats. Immunolabeling for glial fibrillary acidic protein showed significant astrocyte activation in the ipsilateral hippocampus of TBI rats. IL-6 and TNF-α in the core lesion peaked on day 1 postinjury, while those in the ipsilateral hippocampus peaked on day 3. These subsequently gradually declined to sham levels by day 14. It was concluded that GluCEST imaging has potential to be a novel neuroimaging approach for predicting cognitive outcome and to better understand neuroinflammation following TBI.

Amyloid-β (Aβ) deposits and some proteins play essential roles in the pathogenesis of Alzheimer's disease (AD). Amide proton transfer (APT) imaging, as an imaging modality to detect tissue protein, has shown promising features for the diagnosis of AD disease. In this study, we chose 10 AD model rats as the experimental group and 10 sham-operated rats as the control group. All the rats underwent a Y-maze test before APT image acquisition, using saturation with frequency alternating RF irradiation (APT SAFARI) method on a 7.0 T animal MRI scanner. Compared with the control group, APT (3.5 ppm) values of brain were significantly reduced in AD models (p < 0.002). The APT SAFARI imaging is more significant than APT imaging (p < 0.0001). AD model mice showed spatial learning and memory loss in the Y-maze experiment. In addition, there was significant neuronal loss in the hippocampal CA1 region and cortex compared with sham-operated rats. In conclusion, we demonstrated that APT imaging could potentially provide molecular biomarkers for the non-invasive diagnosis of AD. APT SAFARI MRI could be used as an effective tool to improve the accuracy of diagnosis of AD compared with conventional APT imaging.

Aims: To elucidate the possible mechanisms of how basic fibroblast growth factor (bFGF) influences epidermal homeostasis in a living skin equivalent (LSE) model. Methods: Several wound healing-related growth factors were analyzed at protein and mRNA levels for dermal fibroblasts of induced alpha-smooth muscle actin (α-SMA)-positive or α-SMA-negative phenotypes. During culturing an LSE model by seeding normal human keratinocytes on a fibroblast-populated type I collagen gel, bFGF or neutralizing antibody for keratinocyte growth factor (KGF) was added to investigate its effects on fibroblast phenotypes and, subsequently, epidermal homeostasis by histology and immunohistochemistry. Results: The α-SMA-positive phenotype of fibroblasts induced by transforming growth factor beta-1 (TGF-β₁) markedly suppressed the expression of KGF and hepatocyte growth factor (HGF), and slightly upregulated vascular endothelial growth factor (VEGF) and TGF-β₁ at mRNA and protein levels, compared with α-SMA-negative fibroblasts treated with bFGF. α-SMA expression of fibroblasts at the epidermal-mesenchymal junction of the LSEs was suppressed by the addition of bFGF, and a better-differentiated epidermis was presented. The abrogation of KGF from fibroblasts by the addition of the KGF neutralizing antibody disenabled the LSE culturing system to develop an epidermis. Conclusions: bFGF, through affecting the phenotypes and functions of fibroblasts, especially KGF expression, influenced epidermal homeostasis in an LSE model.

To investigate the development of eccrine sweat glands and the expression of Foxa1 genes and proteins in the course of development, the footpads from E15.5 to E21.5, P1-P12, P14, P21, P28 and P56 rats were subjected to immunofluorescence staining of FoxA1 and double immunofluorescence staining of K14/α-SMA, FoxA1/K7 and FoxA1/α-SMA, and were processed for Foxa1 gene detection by RT-qPCR. The results showed that rat eccrine sweat gland germs was first observed emerging from the basal layer of epidermis at E19.5, and then elongated downward into the dermis, forming straight ducts by E21.5. Early development of the secretory segments appeared at P1. The Foxa1 gene was not expressed in rat footpads until P2, but from P2 to P5, its expression up-regulated sharply, and thereafter maintained at a high level until adulthood. FoxA1 protein was first observed at P6 in eccrine sweat glands, four days after initial detection of Foxa1 gene transcripts. In skin, FoxA1-positive cells were present exclusively in secretory coils, with 95% being K7-positive secretory cells and 5% being α-SMA-positive myoepithelial cells. We conclude that Foxa1 can be used as a marker of eccrine sweat glands in skin and also as a marker of secretory coils, and Foxa1 is related to the development of secretory coils.