Stroke Focus

Alkaline phosphatase and the blood-brain barrier (BBB): The BBB is a dynamic structural and functional interface between the brain and the systemic circulation. The primary cellular components of the BBB are brain endothelial cells (ECs), astrocytes, and pericytes. One protein that is highly expressed on brain ECs is tissue-nonspecific alkaline phosphatase (protein: TNAP; gene: Alpl). My laboratory and others have shown that TNAP enzyme activity is highly elevated in brain ECs and to a much lesser extent in ECs from other organs, like the intestine. The significance of TNAP’s elevated enzyme activity in ischemic stroke is not well understood. My laboratory is the first to investigate the importance of TNAP in the pathophysiology of ischemic stroke. My current research investigates the central hypothesis that loss of TNAP enzyme activity in brain ECs contributes to increased BBB permeability, diminished brain EC integrity, and elevated neuroinflammation in ischemic stroke.

Recent Stroke Publications

A. L. Brichacek and C.M. Brown. Alkaline phosphatase: a biomarker for stroke and implications for treatment. Metab Brain Dis. 2018 Oct 4. DOI: http://10.1007/s11011-018-0322-3

N. El Husseini, C.D. Bushnell, C.M. Brown, D. Attix, N. Rost, G.P. Samsa, C.A. Colton, and L.B. Goldstein. Vascular cellular adhesion molecule-1 (VCAM-1) and memory impairment in African-Americans after small vessel-type stroke. (2020) J Stroke Cerebrovasc Dis. 29(4):104646 DOI: 10.1016/j.jstrokecerebrovasdis.2020.104646

A.L. Brichacek, D.C. Nwafor, S.A. Benkovic, S. Chakraborty, S.M. Kenney, M.E. Mace, S. Jun,C.A. Gambill, W.Wang, H. Hu, X. Ren,J.M. Povroznik, E.B. Engler-Chiurazzi, D. Primerano, J. Denvir, R. Percifield, A. Infante, J. Franko, R. Schafer, D.E. Gemoets, C.M. Brown. Experimental stroke induces chronic gut dysbiosis and neuroinflammation in male mice. bioRxiv 2020.04.29.069575 DOI: https://doi.org/10.1101/2020.04.29.069575

Sepsis Focus

Sepsis Publications

D.C. Nwafor, A.L. Brichacek, J.I. Griffith, A.S. Mohammed, B.P. Lucke-Wold, S. A. Benkovic, W.J. Geldenhuys, P. R. Lockman, C.M. Brown. (2019) Targeting the blood-brain barrier to prevent sepsis-associated cognitive impairment. J Cent Nerv Syst Dis. 11:1179573519840652.

A.L. Brichacek, S.A. Benkovic, S. Chakraborty, D.C. Nwafor, W. Wang, S. Jun, W.J. Geldenhuys, A.B. Pinkerton, J.L. Millán, C.M. Brown (2019) Systemic inhibition of tissue-nonspecific alkaline phosphatase alters the brain-immune axis in experimental sepsis. Sci Rep 9, 18788 DOI:10.1038/s41598-019-55154-2

D.C. Nwafor, S. Chakraborty, A.L. Brichacek, Sujung Jun, C.A. Gambill, Wei Wang, E.B. Engler-Chiurazzi, D. Dakhlallah, A.S. Pinkerton, J.L. Millan, S.A. Benkovic, and C.M. Brown. (2020) Loss of tissue non-specific alkaline phosphatase activity in cerebral microvessels is coupled to persistent neuroinflammation and behavioral deficits in late sepsis. Brain Behav Immun. 84: 115-131. DOI: 10.1016/j.bbi.2019.11.016

D.C. Nwafor and C.M. Brown. (2021) A novel role for tissue-nonspecific alkaline phosphatase (TNAP) at the blood-brain barrier (BBB) during sepsis. Neural Regen Res. 16(1):99-100.