Nearly a century ago – in 1920 – the renowned Danish physiologist August Krogh (1874-1949) received the Nobel prize in physiology and medicine for his work on the anatomy and physiology of the capillaries (1). Less than two decades later a young neuroscientist, Mogens Fog (1904- 1990), observed through a cranial window the pial arteries’ response to variations in blood pressure (2). He observed vasoconstriction during blood pressure increase and vice versa during blood pressure decrease, a phenomenon later determined autoregulation by Niels A. Lassen (1926-1997) (3).
In the 1940’es Kety and Schmidt had introduced the use of inert gas for cerebral blood flow measurement. They used inhaled nitrous oxide, N2O for the studies. In the 1950’es the young Danish physicians Niels A. Lassen and Ole Munck developed the method further by introducing radio labeled inert gasses making measurements much easier. They were indeed the first to introduce the use of radio isotopes for blood flow measurements in man. Lassen continued his research on cerebral blood flow and became a leading figure in Danish physiology and Danish neuroscience for the coming four decades.
In the 1960’es Niels A. Lassen together with his colleague David H. Ingvar (1924-2000) from Lund in Sweden introduced a new method allowing for measurement of regional cerebral blood flow, the intra-arterial 85-Krypton or 133-Xenon injection method (4). The method was first applied in animals and soon also in man. Using multiple external scintillation detectors, the regional cerebral blood flow could be measured in multiple parts of the brain. Brain mapping of functional activation became now possible and was introduced for the first time in using this method. Soon it was an established research topic in neuroscience (5).
Niels A. Lassen combined his effort in Denmark with Erik Skinhøj (1918-1983), Professor of Neurology, and together they established a whole school of young researchers. I joined the group a few days after I graduated from Medical School in 1966, wrote my thesis on regional cerebral blood flow in stroke (6) and continued my cooperation with Lassen for the next three decades. The group was soon joined by Jes Olesen working on functional activation and later on migraine, by Gudrun Boysen working on cerebral blood flow during carotid surgery and in stroke, by Tom Bolwig working with flow and the blood-brain barrier, and by Svend Strandgaard working on cerebral blood flow in hypertension. In hypertension the limits of the cerebral autoregulation are shifted towards higher blood pressure levels. The limits of autoregulation are also modulated physiologically, increased by activation of the sympathetic nervous system and of the renin angiotensin system. Autoregulation became one of the major fields of research (7). Research on cerebral blood flow and metabolism became the topic for a new generation of young talented researchers, many of whom are present leaders in Danish neurology and related areas in neuroscience. Among those Allan Andersen, Lars Friberg, Albert Gjedde, Steen Hasselbalch, Marianne Juhler, Gitte Moos Knudsen, Martin Lauritzen, Ian Law, Leif Østergaard and Gunhild Waldemar.
The story of cerebral blood flow research in Denmark is long. It started with basic physiology, spreading to clinical neuroscience, and has for the last half century inspired so many talented researchers that it has had a main impact not only in flow research but on the whole development of Danish neuroscience. Niels Lassen and Erik Skinhøj would have been proud to see what their disciples have achieved.
1. August Krogh. The Anatomy and Physiology of Capillaries. Yale University Press: New Haven. 1922.
2. Fog M. The relationship between the blood pressure and the tonic regulation of the pial arteries. J Neurol Psychiatry. 1938;1:187-97.
3. Lassen NA. Cerebral blood flow and oxygen consumption in man. Physiol Rev. 1959;39:183-238.
4. Lassen NA, Ingvar DH. The blood flow of the cerebral cortex determined by radioactive krypton 85. Experientia 1961;17:42-3.
5. Lassen NA, Ingvar DH, Skinhøj E. Brain function and blood flow. Sci Am. 1978;239:62-71.
6. Paulson OB. Cerebral apoplexy (stroke). Pathogenesis, pathophysiology and therapy as illustrated by regional blood flow measurements in the brain. Stroke 1971;2:327-60.
7. Paulson OB, Strandgaard S, Edvinsson L. Cerebral autoregulation. Cerebrovasc Brain Metab Rev. 1990;2:161-92.
Olaf Paulson is Professor of Neurology at the Department of Clinical Medicine, University of Copenhagen and Neurobiology Research Unit Rigshospitalet, Copenhagen, Denmark