Adrian Corbett, Ph.D.
Address: 152 Biological Sciences II
Phone: (937) 775-2058
Ph.D., University of Miami (Florida), 1984
I have had a variety of research interests, but am currently focused on finding a delayed pharmacological treatment for stroke which improves motor function, with a key interest in having this treatment successfully translate into human clinical trials. Stroke is the primary cause of long term disability, with over 5 million stroke survivors in the United States and an associated cost of more than $50 billion in 2006 care for ischemic (blood clot) stroke victims alone. Nationally, only 3-8.5 percent of ischemic stroke patients received the clot buster drug (recombinant tissue plasminogen activator), which must be given in a short window of time after initiation of stroke. For more than 90 percent of ischemic stroke patients, there exists no standardized treatment in the days following the stroke other than giving aspirin or a statin (which is largely to prevent a recurring stroke).
When I began my research, I looked closely at the stroke research literature to determine why drugs that were successful in stroke animal models failed to translate well in human clinical trials. I became convinced of the following:
Animal models need to be middle aged and have a discrete stroke (5 percent of the hemisphere or less) to better correlate with the human stroke population
- I use middle aged rats with a discrete stroke induced through stereotactic vasoconstrictor (endothelin-1) injections directly into the motor cortex. (Technique modified from the Windle et al paper (2005; Brain Research 1044: 24-32)
Animals models with better blood vessel collateralization are likely to translate better to the human stroke population.
- Most rat strains have very low blood vessel collateralization. I am currently using Sprague Dawley rats, which have a relatively higher blood vessel collateralization in the brain.
Drugs (generic or brand name) that are tested should be the same as those offered to humans and should be given orally (voluntary oral administration is best).
- I have developed a method to reliably give daily drugs (normal generic or brand name drugs) through voluntary oral administration (Corbett et al, 2012. Lab Animals 46: 1-7)
The primary difference between the vast majority of stroke animal models and the models that I am using is the age of animal, the method of stroke induction, and the size of the brain infarct. Aged animals primarily differ from younger animals in their level of innate neurogenesis. Neurogenesis is regulated by different levels of growth factors, which should promote stroke recovery.
- I sought drugs that could stimulate neurogenesis and thus stimulate growth factor production as potential stroke treatments. So that this treatment would be applicable to the majority of stroke patients, I have primarily tested the drugs beginning 20-26 hours after stroke induction and then continuing daily.
We have an abstract submitted to the 2013 International Stroke Conference on this work.
Corbett, A., McGowin, A., Sieber, S., Flannery, T., and Sibbitt, B. 2012. A method for reliable voluntary oral administration of a fixed dosage (mg/kg) of chronic daily medication to rats. Laboratory Animals 46: 1-7
McGowin, A.E., Truong, T.M, Corbett, A.M., Bagley, D.A., Ehrhart, L.M., Bresette, M.J., Weeges, S.T. and Clark, Dave. 2011. Genetic barcoding of marine leeches (Ozobranchus spp.) from Florida sea turtles and their divergence in host specifity. Molecular Ecology Resources. 11(2), 271-278.
Jarnot, M. and A.M. Corbett. 2006. Immunolocalization of NaV1.2 Channel Subtypes in Rat and Cat Brain and Spinal Cord with High Affinity Antibodies. Brain Research 1107: 1-12.
Kramer JW, Ferguson DG, Corbett AM. (2003) Enrichment of triadic and terminal cisternae vesicles from rabbit skeletal muscles. J Membrane Biology 195:9-20. [ View image]
Castaneda-Castellanos DR, Cano M, Wang JKT, Corbett A, Benson D, Blanck JJ, Thornhill WB, Recio-Pinto E (2000) CNS voltage-dependent Na+ channel expression and distribution in an undifferentiated and differentiated CNS cell line. Brain Res 866:281-285.
Kramer JW, Corbett AM (1996) 1996. Comparison of calcium loading and retention in isolated skeletal muscle triads and terminal cisternae. American J Physiology (Cell Physiology vol. 39) 270:C1602-1610.
Ritucci NA, Corbett AM (1995) The effect of magnesium and ATP on depolarization induced calcium release in isolated skeletal muscle traids. American Journal of Physiology (Cell Physiology vol 38) 269:C85-C95.
Kramer JW, Corbett AM (1995) The voltage dependence of depolarization-induced calcium release in isolated skeletal muscle triads. J Membrane Biol 144:217-230.
Jarnot M, Corbett AM (1995) High titer antibody to mammalian neuronal sodium channels produces sustained channel block. Brain Res 674: 159-162.