1850 



HWDIKiciK ill PHYSIOLOGY 



NEUROPHYSIOLOGY III 



istration of glucose either simultaneously or after 



the administration of insulin prevents or alleviates 

 the effects. Thirdly, the same effects are observed in 

 hypoglycemia resulting from hepatectomy (120, 123), 

 and also after the blockage of normal glucose utiliza- 

 tion by administration of apparently a competitive 

 inhibitor, 2-desoxyglucose, despite the elevation in 

 the blood glucose level produced (Morrell & Landau, 

 personal communication ). 



On the other hand, perfusion experiments in 

 isolated tissues have led to contradictory results. 

 In the isolated thoracic spinal cord of the rat, Tschirgi 

 and associates (190) have observed the abolition of 

 reflex responses during glucose-free perfusion but their 

 recovery on restoration of glucose to the perfusate. 

 Grenell & Davics (67), however, have observed no 

 effecl of glucose deprivation on the spontaneous 

 electrical activity or oxygen consumption of a per- 

 fused segment of cerebral cortex maintained in vivo 

 in the cat. Grenell & Wolbarsht (69) have found 

 r\ idence suggesting that the cortical electrical changes 

 produced by insulin are secondary to a direct action 

 of that agent on subcortical structures. Geiger and 

 co-workers (52) have found in the cat brain that 

 during glucose-free perfusion convulsive activity can 

 occur with the same acceleration of oxygen con- 

 sumption as when glucose is present. In fact, even 

 when glucose is present in the perfusate, the in- 

 creased carbohydrate breakdown which then occurs 

 in the brain during convulsions does not require the 

 added oxygen consumed, for it can be entirely ac- 

 counted for by the increased lactic acid production. 

 Thcv interpret these results as indicative of the 

 existence of noncarbohydrate materials in the brain 

 which are oxidized and account for the increased 

 oxygen consumption during convulsions. In previous 

 studies on the same preparation, Geiger and his 

 associates (53) have demonstrated a fall in cerebral 

 oxygen consumption when fructose was substituted 

 for glucose in the perfusate, fructose disappearance 

 within the brain began only after glucose had dis- 

 appeared from the tissues, and then the oxygen con- 

 sumption was greater than could be accounted for 

 by Inn ins,- utilization alone. The additional oxygen 

 was believed to be consumed in the oxidation of 

 glutamate and glutamine in the cortex. 



The results of the perfusion experiments are diffi- 

 cult I" evaluate inasmuch as ihe\ are performed in 

 preparations which can hardly be considered to lie 

 demonstrating normal functions Furthermore, the 

 experiments in the perfused cat brain must always 

 be i.iieinii', scrutinized foi errors arising from the 



inherent difficulties in isolating the cerebral from the 

 extracerebral circulations. At best these studies have 

 demonstrated that the brain is capable of oxidizing 

 substances other than glucose, but it is not oxygen 

 consumption which is believed to be dependent on 

 glucose utilization. Even in man in hypoglycemic 

 coma, cerebral oxygen consumption, although re- 

 duced, goes on despite negligible glucose utilization 

 (103). It is the normal functioning of the central 

 nervous system which requires the oxidation of 

 glucose, and perfused cerebral tissues are hardly 

 adequate to test this relationship. 



RECOVERY FROM EFFECTS OF HYPOGLYCEMIA PRODUCED 



by clucose administration. The administration of 

 glucose during the period of altered functions pro- 

 duced by hypoglycemia rapidly restores these func- 

 tions to normal. In man in insulin coma such 

 restoration can occur within a few minutes (98). Sim- 

 ilarly, the simultaneous administration of glucose can 

 prevent the development of hypoglycemia and its 

 effects by insulin. 



RELATIVE INABILITY OF OTHER SUBSTRATES TO PRODUCE 

 RECOVERY FROM EFFECTS OF HYPOGLYCEMIA. Ill 



hepatectomized animals, the effects of hypoglycemia 

 on behavior or cortical electrical activity, or both, 

 are not counteracted by lactose, inulin, fructose, 

 galactose, hexosediphosphate, ethanol, glyceralde- 

 hyde, lactate, pyruvate, acetate, succinate, fumarate 

 or glutamate (120, 123). Mannose and maltose have 

 been found to restore in these preparations both 

 normal behavior and electroencephalographic ac- 

 tivity, but their effectiveness is believed to be the 

 result of their prior conversion to glucose (120, u ; 

 In the isolated perfused thoracic spinal cord of the rat, 

 Tschirgi and associates (190) have found that the 

 reflex responses which are eliminated by glucose 

 deprivation are restored fully by pyruvate, isocitrate, 

 glutamine, a-ketoglutaratc and glutamate. The effects 

 of the latter two were associated with the appearance 

 of glucose in the perfusate, but in the case of the 

 others there was no obvious reason to suspect any 

 conversion to glucose. In the same preparation 

 oxaloacetate partialis' restored function, alcohol, 

 acetate, lactate, |8-hydroxv, butyrate, fumarate, ma Lite, 

 succinate, epinephrine, Dl.-alanine, 01 -l\ sine, 1 .-tyro- 

 sine, DI. -aspartate, DL-CySteine and 1 -cvstine were 

 without effect, although sonic- of them were reaclilv 

 oxidized. In insulin coma in man, lactate 1 7(1, IQQ), 

 pyruvate (60, 76) and ethanol (59) have been in- 

 effective for restoring consciousness. Mavcr-Gross & 



