D. Ganten – författare

A cross-sectional account of the advances made in the field of cardiovascular medicine, produced as a result of being able to probe the very roots of biological function.

The first two "Brain Heart Conferences" in Jerusalem in 1978 and 1983 were based upon the common interests of clinically orientated neurologists and cardiologists in the problems of centr'al autonomic control and autonomic disturbances of the cardiovascular system. The relatively slow scientific progress, at least clinically, in this area may be due to the fact that neither cardiologists nor neurologists felt competent in both topics. Furthermore, it has become increasingly difficult to have an overall view of the basic research and its clinical applications in this field. New research methods, based on a comtination of morphological, biochemical, and physiological techniques, have enabled the functional differentiation of various areas of the brain and subsequently also of the autonomic nervous system. The simple dualistic concept of an antagonistic sympathetic-parasympathetic regulation of the circulatory system is no longer valid. It is clear that numerous neurotransmitters, in particular the neuropeptides, are involved in a highly differentiated subdivision of the autonomic system. One of the aims of the IIIrd International Brain Heart Conference was therefore to supply a synopsis of the latest developments in basic research undertaken in this field by exceptionally competent scientists, to clinically orientated neurologists and cardiologists, and thus to provide new impulses for clinical research.

The first two "Brain Heart Conferences" in Jerusalem in 1978 and 1983 were based upon the common interests of clinically orientated neurologists and cardiologists in the problems of centr'al autonomic control and autonomic disturbances of the cardiovascular system. The relatively slow scientific progress, at least clinically, in this area may be due to the fact that neither cardiologists nor neurologists felt competent in both topics. Furthermore, it has become increasingly difficult to have an overall view of the basic research and its clinical applications in this field. New research methods, based on a comtination of morphological, biochemical, and physiological techniques, have enabled the functional differentiation of various areas of the brain and subsequently also of the autonomic nervous system. The simple dualistic concept of an antagonistic sympathetic-parasympathetic regulation of the circulatory system is no longer valid. It is clear that numerous neurotransmitters, in particular the neuropeptides, are involved in a highly differentiated subdivision of the autonomic system. One of the aims of the IIIrd International Brain Heart Conference was therefore to supply a synopsis of the latest developments in basic research undertaken in this field by exceptionally competent scientists, to clinically orientated neurologists and cardiologists, and thus to provide new impulses for clinical research.

The first two "Brain Heart Conferences" in Jerusalem in 1978 and 1983 were based upon the common interests of clinically orientated neurologists and cardiologists in the problems of centr''al autonomic control and autonomic disturbances of the cardiovascular system. The relatively slow scientific progress, at least clinically, in this area may be due to the fact that neither cardiologists nor neurologists felt competent in both topics. Furthermore, it has become increasingly difficult to have an overall view of the basic research and its clinical applications in this field. New research methods, based on a comtination of morphological, biochemical, and physiological techniques, have enabled the functional differentiation of various areas of the brain and subsequently also of the autonomic nervous system. The simple dualistic concept of an antagonistic sympathetic-parasympathetic regulation of the circulatory system is no longer valid. It is clear that numerous neurotransmitters, in particular the neuropeptides, are involved in a highly differentiated subdivision of the autonomic system. One of the aims of the IIIrd International Brain Heart Conference was therefore to supply a synopsis of the latest developments in basic research undertaken in this field by exceptionally competent scientists, to clinically orientated neurologists and cardiologists, and thus to provide new impulses for clinical research.

The first publications on the presence of renin, angiotensino­ gen and angiotensin-like material in brain tissue appeared about ten years ago. This coincided with the discovery of new biological actions of angiotensin in the brain and with the reinvestigation of already known central angiotensin effects. The possibility that angiotensin could be generated within the brain itself had therefore exciting implications. With the recent popularity of brain neuropeptides, interest in this area is even increasing. The discovery of renin-like activity as well as angiotensino­ gen and angiotensin in the brain has led, admittedly by inductive inference, to the hypothesis of the existence of a complete endogenous renin-angiotensin system in the brain.1 For several years there was ardent discussion whether such a renin angiotensin system existed in the brain or not. Inductive inference always contains "an irrational element or a creative intuition".2In view of the biological relevance of a brain angiotensin system, deductive testing of the hypothesis was a worthwhile scientific project taken up by a number of investigators As a matter of principle it is not given to science, to reach either truth or falsity, scientific statements can only attain contmous degrees of probability whose unat­ tamable upper and lower limits are truth or falsity. However, several of the early singular statements and results turned out to be reproducible and acceptable. The theory has thus so far passed its test and we have found no reason to discard it.

There is no doubt that a major problem of present day research workers, especially in the life sciences, is the plethora of publications of all kinds, abstracts, short communications, full papers in journals of varying quality, reviews and proceedings of symposia with, in addition, an unprecedented duplication of publications. Even for experts working in the field, it is almost impossible to keep an up-to-date view of all current research articles. The Western grant and career system encourages scientists to publish as much as possible. The editors and publishers of our new series are convinced that the format of Current Topics in Neuroendocrinology leads a way out of this confusion. Each volume is conceived as a concise up-to-date textbook on one well-defined and currently exciting subject. Different from classic textbooks, however, the speed of publication compares favorably with that of many journals; this ensures an immediacy which is im­ possible in textbooks. On the other hand, topics to be included in this series are also sufficiently reliable, with enough work being done to treat them from several aspects. Each volume will supply four to six chapfers treating such a broad topic as neuroendocrinology from several points of view, for example, anatomic, electrophysiologic, endocrine and behavioral views. Wh~re clinical data are immediately available, they will be included. No other 36Iles treating the nervous or endocrine systems provides such a coordinated set of chapters on an interesting topic in each volume.

There is no doubt that a major problem of present day research workers, especially in the life sciences, is the plethora of publications of all kinds, abstracts, short communications, full papers in journals of varying quality, reviews and proceedings of symposia with, in addition, an unprecedented duplication of publications. Even for experts working in the field, it is almost impossible to keep an up-to-date view of all current research articles. The Western grant and career system encourages scientists to publish as much as possible. The editors and publishers of our new series are convinced that the format of Current Topics in Neuroendocrinology leads a way out of this confusion. Each volume is conceived as a concise up-to-date textbook on one well-defined and currently exciting subject. Different from classic textbooks, however, the speed of publication compares favorably with that of many journals; this ensures an immediacy which is im­ possible in textbooks. On the other hand, topics to be included in this series are also sufficiently reliable, with enough work being done to treat them from several aspects. Each volume will supply four to six chapfers treating such a broad topic as neuroendocrinology from several points of view, for example, anatomic, electrophysiologic, endocrine and behavioral views. Wh~re clinical data are immediately available, they will be included. No other 36Iles treating the nervous or endocrine systems provides such a coordinated set of chapters on an interesting topic in each volume.

The most prominent function of the central nervous system is the control of motor functions by rapidly transmitted impulses through efferent cranial and spinal peripheral nerves. Besides electrically transmitted neural impulses, humoral mechanisms with more sustained actions are exercised by the brain and spinal cord to regulate body homeostasis. Thus, the brain may be regarded as an "endocrine gland" discharging neurohormones (peptides) either into the general circulation (neurohypophyseal hormones) or into the hypothalamo-adenohypophyseal portal circulation (releasing and inhibiting hormones). The brain, therefore, which is protected by the blood-brain barrier from disturbing and potentially noxious exogenous and endogenous agents circulating in the blood, has to have certain neurohemal regions beyond this barrier, such as the neural lobe and the median eminence (infundibulum), where neurohor­ mones have free access to the blood stream. To regulate somatic and autonomic functions in the best possible way, the central nervous system is highly dependent on feedback signals conveyed through somatic and visceral afferent nerves as well as on peripheral humoral signals such as peripheral hormones and other circulating substances that are under homeostatic regulation, e. g. , peptides, arnines, electrolytes, and other biologically active agents. In this chapter, the role of the blood-brain barrier in the regulation of these sub­ stances will be discussed with special emphasis on the access through the blood-brain barrier to cardiovascular centers. 2 The Blood-Brain Barrier 2.

The most prominent function of the central nervous system is the control of motor functions by rapidly transmitted impulses through efferent cranial and spinal peripheral nerves. Besides electrically transmitted neural impulses, humoral mechanisms with more sustained actions are exercised by the brain and spinal cord to regulate body homeostasis. Thus, the brain may be regarded as an "endocrine gland" discharging neurohormones (peptides) either into the general circulation (neurohypophyseal hormones) or into the hypothalamo-adenohypophyseal portal circulation (releasing and inhibiting hormones). The brain, therefore, which is protected by the blood-brain barrier from disturbing and potentially noxious exogenous and endogenous agents circulating in the blood, has to have certain neurohemal regions beyond this barrier, such as the neural lobe and the median eminence (infundibulum), where neurohor­ mones have free access to the blood stream. To regulate somatic and autonomic functions in the best possible way, the central nervous system is highly dependent on feedback signals conveyed through somatic and visceral afferent nerves as well as on peripheral humoral signals such as peripheral hormones and other circulating substances that are under homeostatic regulation, e. g. , peptides, arnines, electrolytes, and other biologically active agents. In this chapter, the role of the blood-brain barrier in the regulation of these sub­ stances will be discussed with special emphasis on the access through the blood-brain barrier to cardiovascular centers. 2 The Blood-Brain Barrier 2.

With contributions by Clarke, G.; Lang, R.E.; McKinley, M.J.; Merrick, L.P.; Rascher, W.; Richter, D.; Sofroniew, M.; Unger, T.; Weindl, A.

It is well established that progesterone plays a role in the brain and hypophysis as a facilitator and inhibitor of sexual behavior and gonadotropin release in the female rat (Everett 1961; Caligaris et al. 1971; Brown-Grant and Naftolin 1972; Dorner 1972; Meyerson 1972; Barraclough 1973; Goldman and Zarrow 1973; Mann and Barraclough 1973; Freeman et al. 1976; Feder and Marrone 1977; Goodman 1978; Attardi 1981), guinea pig (Morin and Feder 1974), and primates (Odell and Swerdloff 1968; Spies and Niswender 1972; Yamaji et al. 1972; Karsch et al. 1973; Dierschke et al. 1973; Knobi11974; Clifton et al. 1975). In an attempt to learn whether a specific progesterone uptake mechanism exists in the brain and the hypophysis, the distribution and retention pattern of radioactivity after in vivo injection of labeled progesterone was studied. Early work of Kato (1963) did not show a selective uptake of radioactivity in the hypo- thalamus of immature and estrogen-primed immature rats after injection oflow- specific-activity [14C]progesterone, but some tendency of the reticular formation to take up radiation was observed.Laumas and Farooq (1966) reported that after intravenous administration of labeled progesterone to ovariectomized estrogen- treated rats, radioactivity in the brain and pituitary appeared to show a very slight, insignificant increase 1-2 min after injection, but the uptake pattern was not definite, as had been seen with estradiol. Seiki et al.