. Free Radicals and Cerebral Ischaemia


H. B. Demopoulos et al on Free Radicals and Stroke

My Friend and Colleague Harry Demopoulos and his coworkers first defined the role of reactive oxygen species in Stroke. As Nita et al note, "The concept of generation of free radicals during ischemia was first presented by Demopoulos, Flamm and co-workers....". E.g.:

1) Flamm ES, Demopoulos HB, Seligman ML, Poser RG, Ransohoff J., Free radicals in cerebral ischemia, Stroke. 1978 Sep-Oct;9(5):445-7.

2) Demopoulos, H. B,, Flamm, E. S., Pietronegro, D. D., and Seligman, M. L., The free radical pathology and the microcirculation in the major central nervous system disorders, Acta Physiol. Scand. Suppl., 492, 91, 1980.

This paper is special because it first suggests that free radical pathogenesis in stroke may be at least partially-mediated thru damage to the microcirculation. The neuroprotective antistroke agents Cerovive, Tirilazad, SOD/Catalase, and uric acid all likely work at this level, rather than interneuronally.

3) Demopoulos, H., Flamm, E., Seligman, M. L., Power, R., Pietronegro, D., and Ransohoff, J., Molecular pathology of lipids in CNS membranes, in Oxygen and Physiological Function, Volsis, F. F., Ed., Professional Information Library, Dallas, Tex., 1977, 491.

4) Demopoulos, H. B., Flamm, E., Seligman, M,, and Pietronigro, D. D., Oxygen free radicals in central nervous system ischaemia and trauma, in Pathology of Oxygen, Autor, A. P., Ed., Academic Press, New York, 1982, 127.

"Large doses of methohexital protect the microcirculation in regional cerebral ischaemia models". This is the first well-defined example of an antistroke neuroprotective agent working outside the blood-brain barrier. Cerovive, SOD/catalase, uric acid, and Tirilazad are others.

Papers of Peter H. Proctor with Harry B. Demopolous

1) McGinness, J.E., Proctor, P.H., Demopoulos, H.B., Hokansen, J.A. and Kirkpatrick, D. S. Amelioration of cis-platinum nephrotoxicity by orgotein (superoxide dismutase). Physiol. Chem. and Phys. 10: 267-277, 1978.

2) McGinness, J.E., Proctor, P.H., Demopoulos, H.B., Hokansen, J.A. and Van, N.T. In vivo evidence for superoxide and peroxide production by adriamycin and cis-platinum. In: Pathology of Oxygen. A. Autor, (Ed.). Academic Press, New York, 1982, pp. 191-202.

Presented at the same symposium as the last Demopoulos paper above. I was There.

Keywords: nitrone radical nitroxide cerovive (tm) astrazeneca renovis stroke nxy-059