CENTRAL NERVOUS SYSTEM CIRCULATION, FLUIDS AND BARRIERS 



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neurohypophysis and the adjacent parts of the hypo- 

 thalamus are recognized as the site of formation of 

 specific antidiuretic and oxytocic hormones (14). The 

 pineal body has recently been implicated by Altschule 

 (2) as the site of formation of a substance (probably a 

 peptide) which is capable of inducing more nearly 

 normal behavior patterns in psychotic individuals. 

 The writer knows of no corresponding studies of the 

 other nonneural areas listed above. 



In the case of the area postrema, the situation 

 appears to be relatively simple; blood-borne foreign 

 chemicals which do not readily pass the blood-brain 

 barrier elsewhere can freely enter this region, combine 

 with appropriate chemoreceptors and thus give rise 

 to nerve impulses which excite the vomiting center. 

 The corresponding relations of the neurohypophv sis 

 and the adjacent tissues are less clear, but there is 

 evidence (33) that acetylcholine can trigger the release 

 of the antidiuretic hormone and the same is true of 

 drugs which release histamine (10). The antidiuretic 

 component of the neurohypophyseal secretion, accord- 

 ing to recent findings (32), can activate the elabora- 

 tion or release of adrenocorticotropic hormone by the 

 adenohypophysis. Norepinephrine and epinephrine 

 also have been held to be important activators of the 

 latter mechanism (18) but whether directly or through 

 liberation ofneurohypopliysc.il hormones is ;il present 

 unknown. 



Viewed in this light, the unusually great perme- 

 ability of these parts of the brain may be of great 

 significance in relation to the rapidly developing con- 

 cept of liberation of acetylcholine, norepinephrine and 

 serotonin in the hypothalamus (21 ). The role of hista- 

 mine remains to be established, but its relatively 

 high concentration in this part of the brain is sugges- 

 tive. Apart from their possible role in the local control 

 of cerebral vascular tonus (see the preceding sec- 

 tion), such small molecule agents appear to be able to 

 act as trigger mechanisms in the liberation of larger, 

 more specific molecules such as vasopressin, oxytocin 

 and adrenocorticotropin. The presently controversial 

 'antischizophrenic' agent in the pineal body, if 

 eventually proved to play an important role in the 

 alleviation of abnormal mental behavior, may de- 

 serve study from the standpoint of possible relations 

 of serotonin and norepinephrine to the physiology and 

 pharmacology of the mind (21). The information 

 available for the area postrema indicates the possi- 

 bility that more or less specific reflexes may play a 

 role in some of the functions of these nonneural 

 regions. Direct effects of relatively nonspecific small 

 molecule agents on tissues which elaborate more 



specific peptide or protein hormones may also be 

 considered. The early observations of Cushing (9), 

 indicating that pituitary extract produces strong 

 activation of the parasympathetic centers when in- 

 jected into the cerebral ventricles, also appear to 

 deserve re-examination in the light of the current con- 

 cept that the effects of some of the tranquilizing drugs 

 are a manifestation of preponderance of the para- 

 sympathetic over the sympathetic centers of the 

 brain (34). 



In this connection mention may also be made of 

 another seemingly unrelated recent trend in relation 

 to the central regulation of water and salt balance. 

 Smith (43) has recently presented evidence suggestive 

 of a hypothalamic control of water and salt absorp- 

 tion by the renal tubules as a result of inhibitory im- 

 pulses arising from 'volume receptors' in the pul- 

 monary veins (or left atrium) and the peripheral 

 arterial tree (or tissue spaces). Barorcceptor reflexes, 

 inhibitory to central vasomotor mechanisms, are 

 known to arise from the pulmonary veins and from 

 main peripheral arteries (3); but they have not 

 previously been brought into relation with a con- 

 comitant inhibition of the output of hormones. The 

 agent responsible for regulating the renal tubular 

 reabsorption of water presumably is the antidiuretic 

 hormone of the neurohypophysis. For the correspond- 

 ing conservation of sodium a 'primitive antinatri- 

 uretic hormone' is postulated (43). 



further developments of this interesting idea are 

 to be expected. At present it stands as one more item 

 of evidence of possible — and hitherto unsuspected — 

 relationships anions; nerve impulses, chemical agents, 

 and the regulation of highly specialized functions in 

 the brain and elsewhere. The peculiar structure and 

 permeability relations of the nonneural parts of the 

 brain seem to indicate a special role for them, but this 

 remains to be proved. 



In the preceding discussion it has been assumed 

 that the eventual effects, whether referable to the 

 combination of chemical aejents with chemoreceptors 

 in a "trigger zone,' liberation of chemical mediators 

 by afferent impulses, or alterations in the rate of 

 formation or release of specific peptide or protein 

 hormones, are due to direct intervention of the corre- 

 sponding agents in the specific metabolic reactions of 

 the cells concerned. It is possible that changes in local 

 vascular tonus, dependent on the nature and concen- 

 tration of vasoactive substances, also may play a part 

 in such events. At present there is no information 

 either as to the possibility of such occurrences, or the 

 influences (if any) which they might exert on the 



