i 74 8 



II VNDI'.l )i Ik i >l 11I1 S l.\ 



NEUROPHYSIOLOGY III 



artefact in the latter, or a spotty distribution of the 

 sympathetically induced vasoconstriction of such a 

 nature as to leave total cerebral blood flow unchanged 

 while reducing it in certain limited areas. 



There is at present no evidence upon which this 

 question can be answered. Cerebral angiospasm is 

 frequently advanced as an explanation for transitory, 

 completely reversible clinical derangements, but the 

 only agencv bv which a physiologically significant 

 degree of cerebral vasoconstriction has been produced 

 in man is hyperventilation. It is, of course, possible 

 that a usually rudimentary vasoconstrictor innerva- 

 tion can become abnormally active, and that a nor- 

 mallv sharply localized neurogenic vasoconstriction 

 may involve parts of the brain not ordinarily affected; 

 but of this there is as vet no evidence. 



IMlllVl (IF NEt'ROHl A1HRAI. AGENTS 



Studies of total cerebral blood flow in monkeys 

 indicated that these vessels can be constricted by 

 epinephrine (and other sympathomimetic drugs) and 

 dilated by acetylcholine and histamine, provided that 

 the drugs were injected into the cerebral arterial 

 stream (it). When they were given systemically, 

 cerebral blood flow passively followed the concomi- 

 i.nii changes in arterial pressure. Observations similar 

 to the latter have been made in man with epineph- 

 line (.'7) and histamine (i). Norepinephrine was not 

 tested in the monkey, but it is the only agent (other 

 ill. hi hypocapnia) that has been shown to be able to 

 constrict the cerebral vessels of man (27). 



Such findings are interesting in themselves, but 

 the) acquire new significance in the lighl of recent 

 animal studies which indicate a considerable physio- 

 logical and pharmacological significance for nor- 

 epinephrine, acetylcholine and 5-hydroxytryptamine 

 (serotonin) as chemical mediators in certain parts 

 of the brain (.mi. Ii is noteworthy thai these agents 

 are found in highest concentration in the hypo- 

 thalamic region (21) where the histamine concentra- 

 tion also is highest (13). So far the possible relation- 

 ship of release of such chemicals to local cerebral 

 vascular adjustments appears not to have been con- 

 id) n ( l V 1 1 ■, Id inline and histamine are known to be 



tpable "I dilating the cerebral vessels of animals 

 when applied locally (15, 17, 4H) or injected intra- 

 arleriallx (|iu. Norepinephrine and serotonin were 

 ikpI then available, but since epinephrine (a we.il. 1 



vasoconstrictoi than its demethylated congener) was 

 shown to be a cerebral vasoconstrictoi when so 



administered in animals (11, 40), and since norepi- 

 nephrine is known to be similarly active in man (27), 

 this agent at least should increase cerebral vascular 

 tonus at the site of its liberation. Serotonin has not 

 been studied in this respect, but it is a smooth muscle 

 stimulant in general (12) and it would therefore be 

 expected to act like norepinephrine. 



Thus there is a clear possibility of an intrinsic, 

 localized cerebral vascular regulation by means of 

 vasoactive agents liberated from brain cells. The 

 direction and extent of the resulting change in vas- 

 cular tonus should vary according to the preponder- 

 ance of vasodilator (acetylcholine, perhaps histamine) 

 or vasoconstrictor influences (norepinephrine, pos- 

 sibly serotonin). All these agents are inactivated by 

 appropriate enzyme systems and therefore would 

 exert only brief effects. A mechanism of this type 

 could explain localized cerebral vasodilatation, such 

 as that in the visual cortex on illumination of the eve 

 (40), without involving a vasodilator innervation or a 

 local accumulation of vasodilator metabolites. The 

 situation would be analogous to that seen in the sub- 

 maxillary gland on stimulation of the chorda tympani 

 nerve; both increased secretion and vasodilatation 

 here are attributed to liberation of acetylcholine (4). 

 A corresponding reduction in blood flow in other 

 areas by preponderance of vasoconstrictor agents 

 would provide for a redistribution of blood within 

 the brain with little or no change in total blood flow 

 or total arteriovenous oxygen difference. It might 

 also furnish a basis for localized cerebral angio- 

 spasms. 



TRIGGER ZONES IN THE BRAIN 



In Chapter l.XNII of this Handbook Davson points 

 out that certain parts of the brain are more permeable 

 than others to blood-borne chemicals. Such regions 

 are the area postrema, the paraphysis, the wall of the 

 optic recess, the eininentia saccularis of the hypo- 

 physeal stem, the neurohypophysis and the pineal 

 body. They have in common a lack of neuronal tissue 

 and may be regarded as essentially nonneural parts 

 ol the brain. 



I In- physiological significance of this coincidence 

 (practical absence of the usual blood-brain barrier in 

 parts of the brain that lack the usual structural frame- 

 work ol the organ) is at present unknown, but there 



are a few suggestive pieces ol information. The area 



pOStrema is well established as a site of cheino- 

 receptors for the medullary vomiting center (7). The 



