Research

My research interest is the blood-brain barrier (BBB) which regulates molecular traffic across blood and the brain.  The BBB is formed by brain capillary endothelium.  At CDR, we have established cell culture models using primary brain endothelial cells which allow us to study the BBB function, particularly transport across the BBB.  We are using the models to study mechanisms of BBB permeability, including that of the neurotransmitter glutamate.  Through several collaborative projects, we are utilizing the models for screening of BBB permeable compounds.  We are also looking into alterations of the BBB structure and function in pathological condition.

Current Research Projects:

• The pathophysiology of the BBB in animal model of cerebral hypoperfusion
• Application of in vitro model of the BBB to investigate  detailed permeability mechanisms of Mitragyna speciosa (ketum) alkaloids

People

• Hema A/P Sekaran
• Mahathir Mohd Uzid

Current MSc student (as main supervisor)

• Liyana Mohd Nazri

Publications

1. Yusof, S.R., Mohd Uzid, M., Teh, E.H., Hanapi, N.A., Mohideen, M., Mohamad Arshad, A.S., Mordi, M.N., Loryan, I., Hammarlund-Udenaes, M. (2018) Rate and extent of mitragynine and 7-hydroxymitragynine blood-brain barrier transport and their intra-brain distribution: the missing link in pharmacodynamic studies. Addict Biol. 2018 Aug 8. doi: 10.1111/adb.12661. [Epub ahead of print]
2. Nielsen, S.S.E.,  Siupka, P., Georgian, A., Preston, J.E., Tóth, A.E., Yusof, S.R., Abbott, N.J., Nielsen, M.S. (2017) Improved method for the establishment of an in vitro blood-brain barrier model based on porcine brain endothelial cells. J Vis Exp., 127, e56277.
3. Yusof, S.R., Abbott, N.J., Avdeef, A. (2017) Impact of capillary flow hydrodynamics on carrier-mediated transport of opioid derivatives at the blood-brain barrier, based on pH-dependent Michaelis-Menten and Crone-Renkin analyses. Eur J Pharm Sci., 106, 274-286.
4. Liew K.F., Hanapi, N.A., Chan, K.L., Yusof, S.R., Lee, C.Y. (2017) Assessment of the blood-brain barrier permeability of potential neuroprotective aurones in PAMPA and porcine brain endothelial cell models. J Pharm Sci., 106 (2), 502-510.
5. Yusof, S.R., Avdeef, A., Abbott, N.J. (2014) In vitro porcine blood-brain barrier model for permeability studies: pCEL-X software pK_a^FLUX method for aqueous boundary layer correction and detailed data analysis. Eur J Pharm Sci., 65C, 98.
6. Dickens, D., Yusof, S.R., Abbott, N.J., Weksler, B., Romero, I.A., Couraud, P.O., Alfirevic, A., Pirmohamed, A., Owen, A. (2013) A multi-system approach assessing the interaction of anticonvulsants with P-gp. PLoS One, 8, e64854.
7. Teow, H.M., Zhou, Z., Najlah, M., Yusof, S.R., Abbott, N.J., D’Emanuele, A. (2013) Delivery of paclitaxel across cellular barriers using a dendrimer-based nanocarrier. Int. J. Pharm., 441, 701-711.
8. Abbott, N.J., Patabendige, A.A. Dolman, D.E., Yusof, S.R., Begley, D.J. (2010) Structure and function of the blood-brain barrier. Neurobiol. Dis., 37, 13-25.

Chapter in Book

1. Abbott, N.J., Dolman, D.E.M., Yusof, S.R., Reichel A. (2014) In vitro models of blood-brain barriers, in Drug Delivery to the Brain, Physiological Concepts, Methodologies and Approaches, (Hammarlund-Udenaes M., de Lange E. and Thorne R., (eds.), Vol. 10, pp. 163-197, Springer New York.

Published Abstract

1. Mohd Uzid M, Hanapi N, Mansor S, Yusof S (2016) Mitragynine and 7-hydroxymitragynine: In vitro blood-brain barrier permeability studies. Front. Cell. Neurosci. Conference Abstract: 14^th Meeting of the Asian-Pacific Society for Neurochemistry. doi: 10.3389/conf.fncel.2016.36.00145.
2. Sekaran H, Hassan Z, Yusof S (2016) Regional extravasation of Evans blue dye in the brain across the blood-brain barrier during cerebral hypoperfusion. Front. Cell. Neurosci. Conference Abstract: 14^th Meeting of the Asian-Pacific Society for Neurochemistry. doi: 10.3389/conf.fncel.2016.36.00162.
3. Hanapi N, Yusof S, Adenan M, Tengku Muhammad T (2016) Blood-brain barrier permeability studies of Centella asiatica extract as potential neuroprotective agent. Front. Cell. Neurosci. Conference Abstract: 14^th Meeting of the Asian-Pacific Society for Neurochemistry. doi: 10.3389/conf.fncel.2016.36.00142.
4. Mahathir Mohd. Uzid, Nur Aziah Hanapi, Siti Rafidah Yusof (2014) Development of in vitro blood-brain barrier models using primary brain endothelial cells. Archives of Pharmacy Practice, 5 Supplement 1, S9.