CENTRAL NERVOUS SYSTEM CIRCULATION, FLUIDS AND BARRIERS 



1747 



convulsant dosage) automatically entailed a decrease 

 in cerebral vascular resistance sufficient to produce a 

 marked increase in total cerebral blood flow (41). A 

 similar increase in blood flow in a localized area (the 

 visual cortex) was also demonstrated when the func- 

 tional activity of this region was increased by a 

 physiological stimulus, such as illumination of the 

 eye (40). Since arterial pressure fell in the former case 

 and did not change in the latter, an automatic adjust- 

 ment of cerebral vascular tonus to the metabolic 

 requirements of the tissue was indicated. 



The changes in the cerebral vascular tonus of man 

 at the instant of a convulsion have not been studied 

 as yet because the method generally used is not 

 adapted to fluctuations in pulmonary ventilation. 

 Observations have been made in human subjects .is 

 soon as possible after the resumption of regular 

 breathing following the convulsions of electroshock 

 (26), pentylenetetrazol (26) and epilepsy (19), but all 

 have shown only a decrease in cerebral blood flow 

 and an increase in cerebral vascular resistance at this 

 time. These results can be attributed to the concomi- 

 tant hypocapnia and acidosis (from the antecedent 

 muscular activity) and may be regarded as another 

 manifestation of the preponderance of pCOo over 

 [H + ] when they change in opposite directions. With 

 these assumptions, the findings do not necessarily 

 discredit the original concept, but they certainly do 

 not substantiate it. The question might be answered 

 by experiments on man in whom the muscular move- 

 ments of convulsant agencies were obviated b) 

 curare, decamethonium or succinyl choline, but this 

 rather formidable experiment has not seemed justi- 

 fiable and a better approach would be to use a method 

 capable of revealing instantaneous changes in cere- 

 bral vascular resistance. Localized cerebral vascular 

 adjustments to localized changes in functional activity 

 in the brain also have not been studied in man largely 

 because of lack of a suitable method. 



Other observations in man cast even greater doubts 

 on the validity of the simple concept derived from 

 animal experiments. The increased cerebral activity 

 associated with mental arithmetic caused no measur- 

 able increase in cerebral blood flow (44) and the 

 onset of sleep was associated with an increase rather 

 than a decrease in this function (31). Since there was 

 no concomitant change in cerebral oxygen consump- 

 tion, these findings are not compelling evidence; but 

 they indicate at least that the situation is not as 

 simple as the one postulated from the animal experi- 

 ments. Drugs which depressed cerebral functional 

 activity, such as thiopental (22), alcohol (6) and 



insulin (26), depressed the cerebral oxygen uptake of 

 man; but the cerebral vascular resistance was de- 

 creased, not increased. This discordant finding also 

 may be discounted by attributing it to an inactivation 

 by the drugs of the normally precise intrinsic regulat- 

 ing mechanism of the cerebral vessels. If this is so, 

 the homeostatic mechanisms alluded to above do not 

 operate in anesthetized or comatose man and his 

 brain cells will feel the full impact of changes in the 

 arterial blood gases. Such a suggestion was advanced 

 some years ago to account for the occurrence of vaso- 

 motor depression during hyperventilation under 

 anesthesia (37), but the matter has not been studied 

 further. 



It is evident that there is at present no direct evi- 

 dence to substantiate the concept that the blood 

 vessels supplying brain cells of man automatically 

 alter their tonus in relation to changes in the func- 

 tional or metabolic state of the cells. The speculations 

 in an earlier publication (37) as to the mechanisms 

 li\ which such adjustments are brought about there- 

 fore have lost much of their challenge and have not 

 been pursued further. Recent developments indicating 

 thai vasoactive substances such as acetylcholine, 

 serotonin and norepinephrine are liberated by nerve 

 impulses, at least in some parts of the brain, may 

 necessitate reopening of this question (see below). 



ROLE OF VASOMOTOR NERVES IN THE CONTROL 

 OF THE CEREBRAL CIRCl I VTION 



Experiments on cats indicated that the parts of 

 the brain above the tentorium possess .1 \ asoconstrictor 

 innervation via the cervical sympathetic (37) and a 

 vasodilator innervation carried by the great super- 

 ficial petrosal nerve (8, 16). The pons and medulla 

 showed no signs of the former (37 I, the latter was not 

 tested here. Experiments in man have revealed no 

 sign of a cerebral vasoconstrictor innervation in the 

 corresponding sympathetic pathways (20, 35); the 

 vasodilator innervation has not been studied. It is per- 

 haps significant that measurements of total cerebral 

 blood flow in the monkey failed to give any evidence 

 of cerebral vasoconstriction on stimulation of the 

 cervical sympathetic nerve (11). This observation 

 indicates that the results in cats were not due entirely 

 to the use of an artificial electrical stimulus that has 

 no physiological equivalent, for the same stimulus 

 had no such effect in the monkey. The similarity of 

 the results in man and monkey may indicate a species 

 difference between these and the cat, an instrumental 



