In the past dozen years, newly developed chronic recording techniques have made possible the direct study of peripheral nerve and spinal cord function in conscious, freely moving animals. Two complementary approaches were introduced in the mid-1970s: floating microelectrodes to r ...
In addition to desensitization and downregulation of receptors at the cell membrane, the number of receptors expressed is modulated by regulation of steady-state levels of mRNA and the rate of gene transcription (see refs. 1 and 2 for reviews). Regulation of receptor mRNA and gene transcript ...
A frequently observed adaptive response to chronic agonist occupancy of cell surface receptors is a process in which receptors become internalized or sequestered into a cell compartment to which hydrophilic ligands have only a limited access (1–3). Although receptor sequestration ...
Agonist occupation of G protein-coupled receptors (GPCRs) leads to a cellular response that wanes, or desensitizes, with prolonged agonist exposure. Different cellular mechanisms contribute to desensitization, including the altered function and/or expression of recepto ...
Convection-enhanced drug delivery is a novel technology used to deliver drugs into brain tissue and which is currently evaluated in clinical trials. Drugs are delivered continuously via intracranial catheters and enable to achieve large volume of distributions at high drug concent ...
Recently, the nasal route for systemic drug delivery has gained great interest. It provides several advantages over other routes of drug administrations. These include rapid absorption, avoidance of the intestinal and hepatic presystemic disposition, and high potential for drug t ...
Intracarotid drug delivery was extensively investigated in the past; however, the approach was largely abandoned due to inconsistent benefits. Yet, intracarotid drug delivery is anecdotally used for treating a variety of brain diseases. The rapid advances in endovascular techni ...
Direct central neural axis neuromodulation has become a viable means to treat chronic neurologic disease and injury. Although first described in 1898, technology has only recently allowed for strict modulation and adjustments of drug delivery into the centeral nervous system. Evol ...
This chapter presents a mechanistic approach to in silico prediction of blood–brain barrier penetration by drugs and drug-like molecules. Focus is brought to critical analysis of experimental data used for modeling; several factors affecting data quality are discussed. The main exp ...
In the treatment of central nervous system diseases, therapeutic particles need to breach the blood–brain barrier (BBB) to reach their intended target, and it has long been known that this is a difficult barrier to breach. The barrier is both passive with tight junctions hindering passage of even ...
A major challenge to drug delivery in the brain is caused by the blood–brain barrier (BBB), a composite of endothelial structures that exclude over 98% of small-molecule drugs and almost 100% of large-molecule neurotherapeutics from being transmitted to the brain. Current strategies for ov ...
Blood–brain barrier (BBB) limits drug delivery to the brain parenchyma. The ultimate goal of brain drug targeting technology is to deliver therapeutic agents across BBB. Insulin or transferrin as well as other endogenous peptides undergo receptor-mediated transcytosis or transp ...
Limitation of drug delivery to the central nervous system (CNS) is a major problem in development of successful treatment of CNS disorders. Concepts of blood–brain barrier (BBB), its role in transport of various substances from the blood to the brain, as well as strategies to deliver drugs across t ...
Convection-enhanced delivery (CED) is a method of direct intracerebral parenchymal infusion. It has been previously studied as a mechanism of drug delivery in glioma therapy, which is the focus of this review, and much work has gone into the utilization of this technique. CED can be modeled using s ...
The cerebral microvasculature possesses certain cellular features that constitute the blood–brain barrier (BBB) (Abbott et al., Neurobiol Dis 37:13–25, 2010). This dynamic barrier separates the brain parenchyma from peripheral blood flow and is of tremendous clinical importan ...
Common methods for studying angiogenesis in vitro include the tube formation assay, the migration assay, and the study of the endothelial genome. The formation of capillary-like tubes in vitro on basement membrane matrix mimics many steps of the angiogenesis process in vivo and is used widely ...
Pericytes are perivascular cells that play an important role in the development, maturation, and remodeling of blood vessels. However, studies of this important cell type on vascular remodeling have been hindered due to the difficulty of culturing pericytes in adequate numbers to high pu ...
Endothelial cells make up a minor population of cells in a tissue, but play a major role in tissue homeostasis, as well as in diverse pathologies. To understand the biology of cerebral endothelium, purification and characterization of the cerebrocortical endothelial cell population is hi ...
In vitro models of the blood–brain barrier are useful tools to study blood–brain barrier function as well as drug permeation from the systemic circulation to the brain parenchyma. However, a large number of the available in vitro models fail to reflect the tightness of the in vivo blood–brain barr ...
Blood vessels in the central nervous system (CNS) are unique in forming the blood–brain barrier (BBB), which confers high electrical resistance and low permeability properties, thus protecting neural cells from potentially harmful blood components. Endothelial cells, which form ...
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