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PATOS Research Center

Pathophysiology and Treatment of Stroke

Mission

The Center is dedicated to reducing the burden of stroke by encouraging and supporting innovative interdisciplinary research of the highest scientific standard among TTUHSC School of Pharmacy faculty into the pathophysiology of stroke to identify drug targets and develop strategies and drugs for its prevention and/or treatment.

Current members of the Center

Dr. Ulrich Bickel (Director), Dr. Tom Abbruscato, Dr. Jochen Klein, Dr. Neels Van der Schyf (all TTUHSC School of Pharmacy) are the current members of the Center.

History and Accomplishments

The PATOS-Center was formed less than two years ago by faculty members in the Department of Pharmaceutical Sciences as a nucleus for collaborative basic research in the field of ischemic brain disease. The founding members of the Center (Drs. Abbruscato, Bickel, Klein, Weidanz) came from different areas (neurovascular and endothelial biology, neuropharmacology, immunology) but built a strong collaborative program. They were joined in 2003 by Dr. Van der Schyf, a medicinal chemist who contributes to the interdisciplinary character of the Center.

The Center’s “core facility” consists of a research lab for the “Middle Cerebral Artery Occlusion” (MCAO) method, a standard model in experimental stroke research. The Center members chose the mouse as the species, because it offers better versatility, due to the multitude of transgenic and gene knockout models available. The technical setup of the Stroke lab was complemented by hiring a collaborator with long-time experience in animal models (Dr. A. Mdzinarishvili). As a result, the MCAO model was established within less than 6 months. In the short period of its existence, the Center has taken major steps towards establishing itself as a research endeavor with long-term perspective. The preliminary data shown here has already contributed to a number of grant applications and manuscripts directly related to the Center (see below).

Future Goals

1) Establish novel experimental methods to further boost competitiveness. These include synthesis of drug derivatives, perfection of existing stroke models (e.g. by microdialysis), and the addition of an ischemia/reperfusion model and a model for traumatic brain injury.

2) The Center members will enhance visibility and recognition by presenting their work in publications and presentations on scientific congresses. We expect that the Center will give rise to a minimum of three publications by its members each year. At least one of these publications will come from collaborative projects and will be co-authored by at least two members of the Center.

3) P.I.s will strive to obtain extramural funding for individual projects within three years of membership in the Center. After successful funding of several Center members is obtained, an application for a NIH Program Project will be pursued.

Grants Activity

 Funded

  • “Tobacco Smoke Chemicals and Stroke Alter Brain K+ Efflux”
    1 RO1 NS 046526-01 (Abbruscato) 07/01/04 – 03/31/09
    NIH NINDS
    $250,000/year

Pending

  • “Modulation of Brain-to-Blood Potassium Flux by Nicotine and Stroke Conditions” External Research Program (Abbruscato)
    06/01/04 - 05/31/07
    Phillip Morris
    $186,000/year
  • “Chloride channel blockers as a possible target for neuroprotection: studies with bilobalide as model compound” Submitted to the American Heart Association, Texas Affiliate (Grant-in-Aid) on 01/06/04
    P.I.: Jochen Klein, Ph.D.
    Total amount: $ 124,000 (for two years)
  • “Novel Neuroprotective Cage Amines in Cerebral Ischemia”
    Submitted to the American Heart Association, Texas Affiliate (Grant-in-Aid) on 01/08/04
    P.I.: Neels Van der Schyf, Ph.D.
    Total amount: $ 124,000 (for two years)

Presentations/Publications

1. Abbruscato, T.J., Lopez, S.P. Roder, K.R., and Paulson, J.R. Regulation of BBB Na,K,2Cl-Cotransporter through phosphorylation during in vitro stroke conditions. Journal of Pharmacol. & Exp. Ther . (submitted) 2003.

2. Abbruscato, T.J., Roder, K., Paulson, J., Lopez, S. Thomas, J. Activation of brain endothelial nAChR alters blood-to-brain mediated K + transport during stroke conditions. Cerebrovascular Biology A1, Amarillo, TX, 2003.

3. Bickel, U., and Osburg, B. Differential expression of IkBa and IkBb transcripts in a mouse brain-derived endothelial cell line. 33rd Annual Meeting of the Society for Neuroscience Prog. Nr. 952.19, New Orleans, November 8-12, 2003.

4. Fischer, D., Osburg, B., Bickel, U. (2003) Inhibition of monocyte adhesion on endothelial cells by NF-kB decoy oligonucleotide/polyethylenimine complexes. Controlled Release Society, 30th Annual Meeting , Glasgow, Scotland, July 19-23, 2003.

5. Fischer, D., Osburg, B., Petersen, H., Kissel, T., Bickel, U. Influence of Molecular Weight and PEGylation of Poly (ethylene imine) on Organ Distribution and Pharmacokinetics of Complexes with Oligonucleotides in Mice. Drug Metabolism and Disposition (submitted).

6. Geldenhuys, W.J., Steelman, K., Malan, S.F., Bloomquist, J.R. and Van der Schyf, C.J. (2003) Pharmacological evaluation of pentacycloundecylamine derivatives as novel uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists. Program No. 892.15. 2003 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience .

7. Geldenhuys, W.J., Van der Schyf, C.J., and Malan, S.F. (2003) Screening of novel pentacycloundecylamines for neuroprotective activity. Eur. J. Pharmacol ., 458, 73-79.

8. J. Klein, M. Hilgert, O. Weichel, J. Rupp, S.S. Chatterjee and H. Nawrath (2003) NMDA-induced hippocampal membrane breakdown and its inhibition by bilobalide: role of chloride fluxes. Pharmacopsychiatry 36 Suppl. 1, S78-S83.

9. Malan, S.F., Dyason, K., Wagenaar, B., Van der Walt, J.J., and Van der Schyf, C.J. (2003) The structure and ion channel activity of 6-benzylamino-3-hydroxyhexacyclo-[6.5.0.03,7.04,12.05,10.09,13]-tridecane. Arch. Pharm. Pharm. Med. Chem. , 336, 127-133.

10. Paulson, J., Roder, K., Lopez, S. Thomas, J., Allen, D., Abbruscato, T.J. Nicotine effects on BBB mediated potassium transport during combined hypoxia-reoxygenation. Society for Neuroscience, 33rd Annual Meeting , 2003.

11. Van der Schyf, C.J. (2003) Polycyclic Cage Amines in Neurodegenerative Disorders. Invited presentation at TTU Department of Chemistry and Biochemistry Seminar Series, December 9, 2003.

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