EARLY studies of insulin shock, particularly those by HIMWICH and his collaborators, showed that profound hypoglycaemia is accompanied by a decreased cerebral uptake of glucose and of oxygen from the blood stream. HIMWICH (1951) reviewed these studies and cited much evidence indicating that the behavioural and electrographic manifestations of hypoglycaemia are related to the reduced supply of glucose to the brain and the consequent decrease in available oxidative energy. More recently, GEIGER (1958) and his coworkers found that the perfused brain of the cat is able to function for more than 1 hr without exogenous glucose if a high perfusion rate is maintained ; this finding suggests that the brain can utilize endogenous non-carbohydrate substrates and that hypoglycaemic symptoms are due in part to the accumulation of toxic breakdown products of these substrates. ABOOD and GEIGER (1955) found decreases in the protein, lipid and nucleic acid contents of the perfused cat brain deprived of glucose and an associated accumulation in the perfusing blood of small quantities of nitrogenous substances, especially GABA, glutathione, glutamate and creatine. On the other hand, SAMSON, DAHL, DAHL and HIMWICH (1959) found that insulin shock did not significantly decrease the cerebral proteins in cats, and DAWSON (1950) made the same observation in rats.A number of other cerebral constituents are known to undergo quantitative changes during hypoglycaemia. These include glycogen, acid-soluble phosphates, and certain of the free amino acids and related compounds. Some of these substances represent possible sources of limited amounts of energy, either as oxidative substrates or as phosphorylated intermediates, while others may occur as breakdown products of proteins, lipids, or other substrates. Pertinent reports are cited in subsequent sections of this paper; in general, these chemical changes have not been studied in temporal relation to the development of electrographic abnormality.We have attempted to follow simultaneously the progression of the electrographic and a number of chemical changes in insulin shock, and their reversal on termination of the hypoglycaemia. E X P E R I M E N T A LThe experiments were done on adult male dogs weighing 8-23 kg. Food was withheld for a period of 18-24 hr, after which the cranium was exposed and opened and most of the calvarium was removed, the dura mater remaining intact. Preparation was made for electrographic recording from three cortical areas and for freezing the brain in situ with liquid air. Blood pressure was measured from a cannulated femoral artery in the final stages of the experiment. The details of these procedures have been described (TEWS, CARTER, ROA and STONE, 1963).

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