Under normal physiological conditions, the blood-brain barrier (BBB) is a physical and metabolic partition between the systemic circulation and the microenvironment of the brain, which serves to establish and maintain a highly regulated environment necessary for optimal neuronal function. The BBB is situated at the level of the cerebral microvasculature and is characterized by a lack of pinocytotic activity and the presence of "epithelial-like" tight junctions that allow the endothelium to closely regulate the passage of solutes into and out of the brain. In addition, the BBB has a number of channels and transporters that regulate the passage of nutrients into and wastes and toxins out of the brain. However, these same attributes that are necessary for proper neuronal function create a formidable obstacle for the entry of pharmaceutical agents into the brain; therefore, many CNS-associated pathologies (neurodegenerative diseases, multiple sclerosis, and stroke) are under-treated or not treated at all. My research focuses on two facets of BBB research: improving drug delivery to the CNS and characterizing the functional and structural integrity of the BBB in health and disease
Wolka, A.S., Huber, J.D., and Davis, T.P.. Pain and the blood brain barrier: obstacles to drug delivery. Adv Drug Del Rev. (2003). 55: 987-1006.
Egleton, R.D., Huber, J.D., Campos, C.R., and Davis, T.P.. Differential effects of diabetes on rat choroid plexus ion transporter expression. Diabetes. (2003). 52: 1496-1501.
Huber, J.D., Campos, C.R., Egleton, R.D., Witt, K.A., Guo, L., Roberts, M.J., Bentley, M.D., and Davis, T.P.. Conjugation of low molecular weight poly(ethylene glycol) to biphalin enhances antinociceptive profile. J Pharm Sci. (2003). 92: 1377-1385.
Huber, J.D., Hau, V.S., Mark, K.S., Brown, R.C., Campos, C.R., and Davis, T.P.. Microvascular endothelial cells are resistant to direct exposure of formalin, l-carrageenan, and complete Freund’s adjuvant both in vitro and in vivo. Eur J Pharm. (2002). 450: 297-304.
Witt, K.A., Huber, J.D., Egleton, R.D., and Davis, T.P.. Pluronic P85 block copolymer enhances opioid peptide analgesia. J Pharm Exp Ther. (2002). 303: 760-767.
Huber, J.D., Hau, V.S., Campos, C.R., Egleton, R.D., and Davis, T.P.. Functional and structural analysis of blood-brain barrier tight junctions during a 72 hr exposure to l-carrageenan induced inflammatory pain. Amer J Physiol. (2002). 283: 1531-1537.
Witt, K.A., Gillespie, T.J., Huber, J.D., Egleton, R.D., and Davis, T.P.. Peptide drug modifications to enhance bioavailability and blood-brain barrier permeability. Peptides. (2001). 22: 2329-2343.
Huber, J.D., Egleton, R.D., and Davis, T.P.. Molecular physiology and pathophysiology of blood-brain barrier tight junctions. Trends Neurosci. (2001). 24: 719-725.
Egleton, R.D., Mitchell, S.A., Huber, J.D., Palian, M.M., Polt, R., and Davis, T.P.. Improved blood-brain barrier penetration and enhanced analgesia by glycosylation. J Pharm Exp Ther. (2001). 299: 967-972.
Witt, K.A., Huber, J.D., Egleton, R.D., Roberts, M.J., Bentley, M.D., Guo, L., Yamamura, H.I., and Davis, T.P.. Pharmacodynamic and pharmacokinetic characterization of poly(ethylene glycol) conjugation to met-enkephalin analogue DPDPE. J Pharm ExpTher. (2001). 298: 848-856.
Huber, J.D., Witt, K.A., Hom, S., Egleton, R.D. and Davis, T.P. Peripheral inflammatory pain induces blood-brain barrier tight junction reorganization. Amer J Physiol. (2001). 280: H1241-1248.
Egleton, R.D., Mitchell, S.A., Huber, J.D., Gillespie, T.J., Polt, R., and Davis, T.P. Glycosylation improves peptide bioavailability to the brain. Proc West Pharm Soc. (2000). 43: 113-114