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Leu-Wei Lo

Publications and source records attributed to Leu-Wei Lo.

4 recordsLinked to original sources
PubMed2005

In vivo monitoring of fluorescent nanosphere delivery in anesthetized rats using an implantable fiber-optic microprobe.

An implantable needle-type fiber-optic microprobe was constructed to monitor in vivo fluorescent substances in anesthetized rats. This fiber-optic microprobe was composed of coaxial optical fibers that were catheterized using a thin-wall tube of stainless steel (o.d. approximately 400 microm; i.d. approximately 300 microm). When the fiber-optic microprobe was placed in solutions containing various concentrations of fluorescent nanospheres (20 nm), either in the presence or in the absence of 10% Lipofundin acting as an optical phantom, we observed nanosphere concentration-dependent responses of the fluorescence intensity. The microprobe was then implanted into the livers and brains of anesthetized rats to monitor the in situ extravasation of preadministered fluorescent nanospheres from vasculature following the hepatic and cerebral ischemic insults. Both types of ischemic insults showed immediate increases in fluorescent intensities when 20-nm fluorescent nanosphere were administered, but neither ischemic insult induces such an increase when we administered 1000-nm fluorescent nanospheres. Additional experiments can be performed to further narrow the size range of the increase in blood vessel permeability following ischemic insult; such "size" information may be valuable when formulating drugs for optimal local delivery. Although a wide variety of fluorescent substances are used intensively for in vitro biological studies, the in vivo and in situ monitoring of these substances is studied much less often, probably because of difficulties in the efficient assembly of miniaturized fiber optics to detect the relatively weak fluorescence signal arising within such a turbid medium as tissue. To our knowledge, the use of our implantable fiber-optic microprobe is the first minimally invasive technique capable of investigating the "size window" of vascular permeability for the in vivo delivery of nanospheres in both ischemic livers and brains.

Anesthesia↗
PubMed2004

Nanoparticle-based in vivo investigation on blood-brain barrier permeability following ischemia and reperfusion.

The blood-brain barrier (BBB) represents a significant impediment to a large variety of central nervous system-active agents. In the current study, we applied fluorescent polystyrene nanospheres (20 nm) to study the BBB permeability following cerebral ischemia and reperfusion. A microdialysis probe was implanted in the cerebral cortex of an anesthetized rat injected with fluorescent polystyrene nanospheres. The circulating nanospheres extravasating to the brain extracellular fluids were collected by the probe. Fluorescence intensity in the microdialysates throughout the course of cerebral ischemia/reperfusion was measured. Cerebral ischemia and reperfusion induced transient accumulations of extracellular nanospheres in the brain. The accumulation of nanospheres may result from their extravasation from the blood vessels. The concurrent cerebral oxygen levels monitored using oxygen-dependent quenching of phosphorescence decreased following ischemia and returned to their original levels after reperfusion. In conclusion, we demonstrated that high temporal resolution measurements of BBB permeability in vivo can be obtained using fluorescence polystyrene nanospheres and that these data correlate with changes of cerebral oxygen concentration. This present investigation indicates that nanoparticles have potential clinical applications involving drug delivery and determination of therapeutic efficacy and on-site diagnosis.

Animals↗
PubMed2002

Shear stress inhibits adhesion molecule expression in vascular endothelial cells induced by coculture with smooth muscle cells.

Vascular endothelial cells (ECs), which exist in close proximity to vascular smooth muscle cells (SMCs), are constantly subjected to blood flow-induced shear stress. Although the effect of shear stress on endothelial biology has been extensively studied, the influence of SMCs on endothelial response to shear stress remains largely unexplored. We examined the potential role of SMCs in regulating the shear stress-induced gene expression in ECs, using a parallel-plate coculture flow system in which these 2 types of cells were separated by a porous membrane. In this coculture system, SMCs tended to orient perpendicularly to the flow direction, whereas the ECs were elongated and aligned with the flow direction. Under static conditions, coculture with SMCs induced EC gene expression of intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and E-selectin, while attenuating EC gene expression of endothelial nitric oxide synthase (eNOS). Shear stress significantly inhibited SMC-induced adhesion molecule gene expression. These EC responses under static and shear conditions were not observed in the absence of close communication between ECs and SMCs, and they were also not observed when ECs were cocultured with fibroblasts instead of SMCs. Our findings indicate that under static conditions, coculture with SMCs induces ICAM-1, VCAM-1, and E-selectin gene expression in ECs. These coculture effects are inhibited by shear stress and require specific interaction between ECs and SMCs in close contact.

Cell Adhesion Molecules↗