The life of Bo K. Siesjö, MD, PhD, 1930–2013

Authors


Sadly, Bo K. Siesjö died on June 27, 2013, at age 83 years. Bo Siesjö (Fig. 1) was an exceptional neuroscientist who worked tirelessly toward understanding human cerebral blood flow, metabolism, and function under both physiological and pathophysiological settings. His work has influenced stroke therapy and clinical practice, and he will be remembered as a pioneer of experimental brain research. One of his unique skills was the ability to form novel hypotheses from results gathered, and his works on regulation of acid bases in the brain and ischemic pathology are testament to that. He actively promoted translational research, using experimental models to improve acute stroke therapy and patient outcome.

Figure 1.

Bo K. Siesjö (right), Gary K. Steinberg (middle), and Alastair M. Buchan (right) discussing stroke-related research at the Maturation Phenomenon Conference, New Orleans, in 1999.

Born in Ljusdal, Sweden, a young Bo Siesjö entered medical school at Lund University in 1951. By 1958, he had obtained both an MB and MD, and began his PhD by investigating methods by which gases such as carbon dioxide and oxygen could be measured in brain tissue [1]. These measurements are critical for understanding cerebral metabolism, and his early papers paved the way for exciting new research by which the metabolic function of these gases could be investigated. He completed his PhD in 1962 and upon becoming a Research Associate began a 50-year relationship with the Faculty of Medicine at Lund University. During this time, he made critical observations regarding brain carbon dioxide levels and cerebral blood flow [2], and regulation of pH in the brain [3]. From 1966, he became a Career Investigator funded by the Swedish Medical Research Council and continued his research into cerebral metabolism. He began to study cerebral hypoxia and ischemia and their effects on cerebral blood flow, brain metabolism, and the energy state of the brain [4, 5]. In addition, he made critical measurements of cerebral blood flow and cerebral metabolic rate of oxygen in the rat brain [6] which are still used by scientists in physiological studies today. One of his key early findings was the discovery that the enzyme tryptophan hydroxylase (which is part of the serotonin synthesis pathway) has dependence on oxygen, and that hypoxia can adversely affect monoamine neurotransmitter metabolism [7].

Bo Siesjö had developed an exceptional scientific record and was a well-respected basic neuroscientist with a clinical background trying to understand the body's most complicated biology. In 1974 he became Professor in Neurochemistry at the Swedish Medical Research Council and founded the Laboratory of Experimental Brain Research at Lund University. In 1976, he discovered that hypothermia which was protective to the brain, following profound hypoxia, worked by two mechanisms; hypothermia allows total oxygen levels to be higher in times of depleted oxygen, and the cerebral metabolic rate of oxygen is reduced and therefore reducing the cell's energy requirements [8]. Not only did he have an interest in cerebral blood flow and metabolism following hypoxia or ischemia, but he also investigated other pathological conditions such as epilepsy [9], hypoglycemia [10], hypercapnia [11], and spreading depression [12]. He also investigated oxidative stress, the cell's antioxidant response and mitochondrial function following cerebral ischemia [13, 14].

In 1978, Bo Siesjö published a seminal textbook called ‘Brain Energy Metabolism’ [15]; this was considered the bible of cerebral metabolism and stroke research for many years, demonstrating the wide breadth of his theoretical and applied knowledge of physiological neurochemistry. In 1979, he became the Director of the Physiological Research Department at the University Hospital of Lund, and in 1981, was a co-founder of the International Society for Cerebral Blood Flow and Metabolism, and helped initiate the new Journal of Cerebral Blood Flow and Metabolism (JCBFM) as its first Deputy Chief Editor. At this time, his hypotheses on mechanisms by which cells died following cerebral ischemia, such as lactic acidosis [16] increased intracellular Ca2+ concentration [17] and free radical damage [18], were highly influential.

Bo Siesjö's two most cited papers (>1500 citations) have had an enormous impact on the stroke field and led to the two major attempts to ameliorate acute stroke clinically; one, thrombolysis, and the other, neuroprotection. Bo Siesjö (along with Astrup and Symon) published a seminal paper in Stroke in 1981, which outlined the concept of the ischemic penumbra [19]; this, in turn, justified thrombolytic intervention and set up the possibility that neuroprotective drugs would be able to salvage this tissue. The basis of the stroke neuroprotection field is based on his in-depth discussion of the mechanisms of ischemic cell death published in 1981 in the second ever issue of JCBFM [20]. The challenge has been to match thrombolysis with a neuroprotective agent. Bo Siesjö, in many ways, started a holy grail which continues.

After characterizing the critical mediators of the pathophysiological cascade leading to cell death following cerebral ischemia, Bo began to explore potential ways to protect the brain by targeting these factors pharmacologically. He found that calcium channel blockers [21], free radical scavengers [22, 23], and immunosuppressants [24] all showed amelioration of cell death following cerebral ischemia using various animal models. He also showed that reperfusion itself could salvage penumbral tissue following cerebral ischemia [25]. In addition to the mechanisms of primary ischemic damage, he also assessed whether reperfusion injury was due to the damaging effects of reactive oxygen species [26], and outlined the secondary wave of ischemic damage led by a significant inflammatory response, programmed cell death, and protein synthesis reduction [27].

In 1991, Bo Siesjö founded and directed the Experimental Research Centre at the Lund University Hospital, a translational research facility that spanned several clinical disciplines. In 1995, he retired and became Emeritus Professor at Lund University and moved to Honolulu, Hawaii, to become the Director of Research at the Neuroscience Institute, Queen's Medical Centre, where he remained until 2000.

Bo Siesjö was a member of numerous societies, including the European and International Societies for Neurochemistry, International Society for Cerebral Blood Flow and Metabolism (president 1985–1987), Stroke Council of the American Heart Association (honorary member from 1980), American Neurological Association (honorary member from 1988), European Society for Neuroscience, and the New York Academy of Sciences. He was Deputy Chief Editor of the JCBFM (1981–1985) and served on the editorial boards of many other scientific journals. He received a number of scientific prizes for his achievements, including the Mihara Prize in Cerebrovascular Disease (Tokyo, Japan, 1989), J. Allyn Taylor International Prize in Medicine (London, Ontario, Canada, 1992), the K. Zulch Prize in Neurology (Max Planck Society, Germany, 1992), the Hilda and Alfred Eriksson Prize (Royal Swedish Academy of Science, Stockholm, 1994), and the Lifetime Achievement Award for the International Society for Cerebral Blood Flow and Metabolism (Calgary, 2003).

He has authored or co-authored over 500 peer-reviewed articles, and is considered one of the most highly cited medical scientists in the world. Bo Siesjö, along with Fred Plum and Henry Barnett, have been recognized for their seminal contributions to stroke research in the latter part of the 20th century. The passing of Bo Siesjö is a loss to our field; he is a very unique individual whose basic science contribution affected the way we think about our patients, which was Fred Plum's specialty, and the way in which we set up clinical trials, Henry Barnett's specialty. Together the three of them changed our field. Bo Siesjö shone a light by using basic science that underpins the stroke research that all of us are now engaged in. Most of us struggle for our place, albeit transiently, in the sun. For the last 50 years, Bo Siesjö was the sun.

Ancillary