The brain is characterized by an extremely rich blood supply, regulated by changes in blood vessel diameter and blood flow, depending on metabolic demands. The blood–brain barrier (BBB)—a functional and structural barrier separating the intravascular and neuropil compartments—characterizes the brain's vascular bed and is essential for normal brain functions. Disruptions to the regional cerebral blood supply, to blood drainage and to BBB properties have been described in most common neurological disorders, but there is a lack of quantitative methods for assessing blood flow dynamics and BBB permeability in small blood vessels under both physiological and pathological conditions. Here, we present a quantitative image analysis approach that allows the characterization of relative changes in the regional cerebral blood flow (rCBF) and BBB properties in small surface cortical vessels. In experiments conducted using the open window technique in rats, a fluorescent tracer was injected into the tail vein, and images of the small vessels at the surface of the cortex were taken using a fast CCD camera. Pixel-based image analysis included registration and characterization of the changes in fluorescent intensity, followed by cluster analysis. This analysis enabled the characterization of rCBF in small arterioles and venules and changes in BBB permeability. The method was implemented successfully under experimental conditions, including increased rCBF induced by neural stimulation, bile salt-induced BBB breakdown, and photothrombosis-mediated local ischemia. The new approach may be used to study changes in rCBF, neurovascular coupling and BBB permeability under normal and pathological brain conditions.
A lipid material extracted from the omentum has previously been shown to contain a potent angiogenetic activator (20), capable of creating intense vasoproliferation in traumatized tissues (19). This study was undertaken to analyze the efficacy of local administration of this omental lipid fraction on osseous vascularization and bone repair. An osteoperiosteal segmental femoral defect in the rat was replaced by a demineralized allogenic bone graft exposed to continuous local delivery of omental lipid via an implanted miniosmotic pump. Saline solution delivered in the same way served as a control. Neovascularization and bone formation in the transplant were quantitatively evaluated by means of dynamic radioisotopic bone imaging, radiographic photodensitometry, microangiography, and biomechanical testing. Compared with the control group, the omental lipid angiogenic fraction-treated specimens showed an 80% overall increase (p less than 0.001) in bone density as well as a twofold increase (p less than 0.001) in regional blood perfusion, maximal at 2 weeks following surgery. At 12 weeks, biomechanical testing demonstrated significantly higher union rate (p less than 0.05) and strength (p less than 0.01) in the treated specimens as compared with the controls. These data demonstrate that the omental lipid fraction factor has potent angiogenic properties that enhance bone blood perfusion and bone regeneration.
Surface doping of graphene with redox-active molecules is an effective approach to tune its electrical properties, in particular for application as transparent electrodes. Here we present a study and application of surface n-doping of graphene with the molecular reductant (pentamethylcyclopentadienyl)(1,3,5-trimethylbenzene)ruthenium dimer ([RuCp*Mes]2). Photoemission spectroscopy and carrier-transport measurements are combined to investigate doping-induced changes in the electronic structure of the interface between graphene and phenyldi(pyren-2-yl)phosphine oxide (POPy2), which is a low-electron-affinity material that has been used as an electron-transport layer (ETL) in organic light-emitting diodes. Photoemission and Hall voltage measurements confirm the n-doping of graphene. Doping with 1–2 nm of [RuCp*Mes]2 reduces the graphene work function by 1.8 eV and the electron injection barrier by more than 1 eV, enhancing electron injection into POPy2 by several orders of magnitude. Graphene/POPy2/Al diodes with doped graphene cathodes exhibit reasonable stability in both nitrogen and air. These results represent a significant step toward the use of graphene as a transparent cathode for organic devices in general and for OLEDs in particular.
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