Obviously, these are the pathways that should be targeted to induce a brief and reversible increase in BBB permeability for the safe delivery of CNS drugs. It is known that exogenous 9-methoxycamptothecine application of VEGF can increase vascular permeability in peripheral organs, so there are potential risks for non-neurological adverse events, particularly in patients at high risk for hemorrhage. Neoplasia is also a major concern because of its association with neovasculation but this may be obviated by recently developed targeted delivery systems for VEGF. These systems may allow for delivery of high VEGF concentrations to specific regions, reducing the risk of CNS and peripheral hemorrhage. It may also be possible to specifically alter VEGF serum half-life by protein modification to further minimize side effects and maximize efficacy. As for concerns about neoplastic diseases, there is no direct evidence that elevated VEGF concentration alone leads to neoplasms, although caution is still warranted. On the contrary, VEGF signaling can promote functional recovery from stroke in rats but does not increase cancer risk in otherwise health mice. We conclude that single, low-dose VEGF may facilitate CNS drug delivery through the BBB. In future studies, we will design a series of molecular probes of different sizes to monitor BBB permeability dynamically in vivo and determine the exact time window for drug delivery. This study is a major step toward clinical translation of this VEGF protocol for Glycitin improving the pharmacological treatment of brain diseases. There are, however, several limitations to this study. First, the experiments were conducted on healthy mice and certain diseases do significantly affect basal BBB permeability and the response to VEGF. Second, the precise molecular mechanisms for VEGF enhancement of BBB permeability were not determined. Further investigations are needed to more accurately define the relationship between VEGF dose and the change in BBB permeability. Biosensors promise rapid, sensitive and selective estimation of a wide range of analytes. Bioluminescence resonance energy transfer is a form of Fo��rster resonance energy transfer, the non-radiative transfer of energy from an excited state donor to a ground state acceptor, which can be used to transduce biosensor activation into a machine-readable format. Compared to amplitude-based measurements, the ratiometric nature of Fo��rster resonance energy transfer reduces signal variability from a variety of sources including variations in assay volume, minor temperature variations and time dependent signal decay. RET-based reactions are homogeneous and can be performed in 
the fluid phase without solid-phase attachment. This allows for detection of analytes in the fluid phase or particulate suspensions in fluids, without the need for separation. This has many advantages, including the ability to make continuous measurements in a flow format, without having to regenerate a sensing surface, as required, for example by surface plasmon resonance based biosensors. BRET occurs naturally in marine organisms such as Aequorea victoria and Renilla reniformis.