CHEMICAL ENVIRONMENT OF THE CENTRAL NERVOUS SYSTEM 



.883 



rate of glucose transport across cell membranes gen- 

 erally (102), does not penetrate into the brain from 

 the blood (67); but when added to the perfusion fluid 

 in perfusion experiments, it slightly increased the rate 

 of sugar oxidation by the brain (4). 



Glucose and Brain Function 



The dependence of the brain on a minute-to- 

 minute supply of glucose from the blood for main- 

 tenance of function and electrical activity has become 

 an axiom of neurophysiology (see the preceding chap- 

 ter in this volume by Sokoloff). The use of insulin 

 hypoglycemia in schizophrenia (133) has provided 

 dramatic evidence for this relationship in humans 

 Following a shock dose of insulin there develops a 

 series of clinical changes first described by von Angvul 

 (153) and Frostig (48). The signs and symptoms seem 

 to show progressive allocations down the ncuraxis, 

 starting with the cerebral cortex and proceeding 

 towards the medulla oblongata, as shown in the fol- 

 lowing: 



The Five Phyletic 'Layers' (771 



1. Depression of cerebral hemispheres and cerebellum 



2. Release of subcorticodiencephalon 



a. Subcortical motor nuclei 



b. Thalamus 



c. Hypothalamus 



3. Release of midbrain 



4. Release of upper medulla 



5. Release of lower medulla 



Himwich (77) describes the course of events as follows: 

 "The first constellation of signs indicates a depres- 

 sion of cortical functions, for example, disturbances of 

 vision and audition occur as the patient, drooling 

 saliva, becomes drowsy and relaxed, and finally loses 

 contact with his environment. Just before loss of 

 environmental contact some patients exhibit a period 

 of wild excitement. Once contact is lost the second 

 stage begins as an entirely new clinical picture is 

 exhibited. In addition to motor restlessness there are 

 primitive movements of many kinds, grimacing, 

 sticking out the tongue, and kissing, .is well as forced 

 gasping. At this time sensor) stimuli usually evoke 

 exaggerated responses. Release of the autonomic with 

 sympathetic predominant over parasympathetic is 

 marked and comes on in waves as indicated by in- 

 creases in blood pressure and heart rate, flushing of 

 face, dilatation of pupils, and periodic exophthalmus. 

 It is significant that when convulsions do occur they 

 appear most frequently when the second phyletic 



layer is released from cortical control. First fine 

 myoclonic twitchings of the facial muscles are ob- 

 served and then the eyes may deviate to one side. If 

 the larger muscles are seized by contractions which 

 become generalized the patient undergoes grand mal- 

 like convulsions. But in most instances these convul- 

 sive episodes do not appear and the patient graduallv 

 loses these signs and sinks to the third or mesencephalic 

 phase. This complex tells of the release of midbrain 

 functions reminiscent of the changes observed with 

 high decerebration, namely, tonic spasms with flexion 

 of the arms and extension of the legs. Sometimes the 

 patient twists himself on his long axis in torsion 

 spasms. With each paroxysm blood pressure and heart 

 rate increase .... Next signs of low decrebration 

 referable to upper medulla are visible. The legs are 

 still extended, but now the arms are brought back 

 over the head, thus in a remarkable wa\ resembling 

 the decerebrate" rigidit) produced by surgical opera- 

 tive intervention in lower mammals. Finally the fifth 

 stage appears when the medullary (enters are affected 

 by the hypoglycemia. The patient is pallid, the heart 

 raie is slow, respiration is shallow and retarded in rate, 

 pupils are constricted and heal loss is increased." 



Administration of carbohydrate causes the patiem 

 to retrace his symptomatic progression in the reverse 

 direction. Further support for the conclusion of 

 successive syndromes was provided b) Hoagland 

 it id. (80) who demonstrated that cortical electrical 

 iisp,, uses in dogs failed earlier than hypothalamic 

 during progressive hypoglycemia. However, the con- 

 sensus of most observers is that, except for the initial 

 drop in blood sugar until the patient loses contact with 

 his environment, there is little correlation between 

 the symptoms of hypoglycemia and the amount of 

 glucose in the blood. 



These observations have been interpreted as 

 indicating the necessity lor maintaining some mini- 

 mum concentration of glucose in the neuronal 

 milieu, since it has been repeatedly demonstrated that 

 the only energy-yielding substance taken up from the 

 blood by the brain, in amounts large enough to satisfy 

 its energy requirements, is sjlucose (76). However, 

 during perfusion experiments of the suprasylvian 

 gyrus of the cat using glucose-free oxygenated Ringer- 

 albumin solution, it was observed that the perfused 

 cortex maintained its excitability and its oxygen con- 

 sumption for up to 2 hr. (59). Equally surprising are 

 the results of Geiger et al. (50) who report that the 

 isolated perfused cat brain can be maintained with 

 normal electroencephalograms and reflex activitv for 

 1 ' ■_) hr. using a glucose-free perfusate, provided that 



