Time-Series Insulin Treated Data


Blood-brain barrier (BBB) is a monolayer of endothelial cells that line brain capillaries. Protein assemblies arranged in a complex architecture, seal the junctions between the endothelial cells, to prevent passive diffusion of solutes between blood and brain. Moreover, the transendothelial transport of solutes is also heavily restricted. The BBB protects brain by blocking the entry of harmful substances from blood and shielding the brain from peripheral fluctuations in hormones, fatty acids and electrolytes. Thus doing, the BBB achieves highly regulated environment in the brain, which is critical for optimal neuronal function. Such a well-guarded BBB architecture also poses a formidable barrier to the delivery of drugs contrast agents to brain for the diagnosis and treatment of various neurological diseases.

In addition to functioning as a formidable barrier, the BBB serves as a major conduit for the delivery of crucial nutrients and growth factors needed for the upkeep of brain physiology. Moreover, the BBB aids in the clearance of metabolites from the brain. To achieve these distinct functions, the BBB endothelium is highly specialized in handling material transport and cellular signaling. The high fidelity cellular apparatus of BBB endothelium sense changes in the brain and plasma compartments, exchange signals with other members of the neurovascular unit, and is capable of promptly adjusting the material and information transfer between blood and brain compartments.

Owing to these unique functions, any functional and structural impairment of the BBB could lead to disastrous pathophysiological consequences in the brain. BBB dysfunction is implicated in several brain disorders including Alzheimer’s disease, parkinson’s disease, cerebral amyloid angiopathy, stroke, and vascular dementia. Hence, the research community has been actively investigating the cerebrovascular contributions to neurological diseases with major emphasis on the BBB. On the other hand, monumental efforts are being invested in discovering methods to transiently disrupt the BBB to improve drug delivery to the brain. The success of these efforts is heavily dependent upon the availability of reliable in vitro as well as in vivo BBB models.

The human cerebrovascular endothelial cells (hCMEC/D3) described in the current work serves as one such in vitro model that can be easily cultured and manipulated in the lab. The, hCMEC/D3 cell monolayers are widely used in BBB research. The barrier properties and the expression of several classes of receptors, transporters, and enzymes in hCMEC/D3 cells have been validated in previous publications. However, a comprehensive genomic landscape of hCMEC/D3 cells, which is required for investigating molecular mechanisms using systems biology approaches, is not currently available. The current database attempts to fill this important information gap.

July 2014 - Present