Abstract— The question of a constant density of glial cells in mammalian cerebral cortex regardless of species was examined by surveying the cortical activities of two enzymes primarily localized to dial cells. The cortical activity of butyrylcholinesterase (EC 3.1.1.8) was essentially constant at a rate of approx. 0.1 μmol of butyrylthiocholine hydrolysed min‐1 g‐1 over the range of species from rat (brain wt., 1.6 g) to fin whale and sperm whale (brain wt., 6800 and 7800 g, respectively). Over the same range the activity of cortical acetylcholinesterase, a neuronal enzyme, decreases by a factor of 7. Thus, butyrylcholinesterase ranged from < 2 per cent (in small rodent brains) to approximately 10 per cent (in whale brain) of the cortical acetylcholinesterase activity. The cortical activity of carbonic anhydrase (EC 4.2.1.1) was constant at a rate of 6.2 (± 0.25) μmol of CO2 evolved min‐1 g‐1 over the range of species from guinea‐pig (brain wt., 4.75 g) to fin whale (brain wt., 6800 g). These data obtained by assaying the dehydration reaction were confirmed by limited assays of the esterase activity of the enzyme (with p‐nitrophenylacetate as substrate) and agreed with limited, previously reported data for the hydration reaction. Thus, the circumstantial evidence strongly favoured a relative constancy of cortical glial cell density regardless of species. The rates of anaerobic glycolysis in the cerebral cortex of various species were also investigated. For six species from mouse (brain wt., 0.4 g) to beef (brain wt., 380 g) cortical anaerobic glycolysis varied only slightly in the range of 50–62 μmol of CO2 evolved h‐1 g‐l, whereas cortical oxygen consumption for the same range of species decreased by a factor of 3. Previously frozen samples of beef cortex glycolysed at 35 per Cent of the rate of fresh (unfrozen) samples. Since identical rates were obtained for previously frozen samples of fin whale cerebral cortex, we concluded that the relative constancy of cortical anaerobic glycolysis could be extended to the range from mouse to whale and that this aspect of cortical metabolism is probably primarily glial in localization. Some implications of the latter conclusion for the proposed role of astrocytes as modulators of neuronal activity have been discussed.

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PREVIOUS iiivestigations have characterized 2-deoxy-~-glucose* as an inhibitor of glucose metabolism. Its effectiveness in inhibiting glycolysis and growth of neoplastic tissues (ELY, 1954;WOODWARD and HUDSON, 1954;SOKOLOFF et al., 1956; BALL, WICK and SANDERS, 1957) suggested clinical applications. During evaluations of its toxicity in animals preliminary to such trials, LANDAU and LUBS (1958) observed neurological signs and symptoms which closely resembled those of insulin-induced hypoglycaemia.After oral or parenteral administration, 2-deoxyglucose is rapidly distributed throughout the body and appears promptly in the cerebrospinal fluid (WICK, DRURY and MORITA, 1955; LANDAU and LUBS, 1958). Using doses of the order of 12 m-moles/kg, LANDAU and LUBS (1958) found an elevation of blood glucose to levels two or three times normal control values. Under such conditions both blood glucose and 2-deoxyglucose respond to insulin (WICK et al., 1955), but the insulin-mediated decrease in blood glucose to normal ranges intensifies the apparent hypoglycaemic picture. These observations are consistent with inhibition of tissue utilization of glucose in the presence of 2-deoxyglucose, resulting in a situation of simultaneous hyperglycaemia and cytoglycopenia, which in the central nervous system is expressed as dysfunctions usually associated with hypoglycaemia.2-Deoxyglucose is readily phosphorylated by yeast, muscle and brain hexokindse (SOLS and CRANE, 1954;WOODWARD and HUDSON, 1955;WICK et al., 1957), and it produces inhibition of glycolysis in yeast and various mammalian tissues, including brain (WOODWARD, 1952;WOODWARD and HUDSON, 1954). Metabolism of 2deoxyglucose-6-phosphate appears not to occur (SOLS and CRANE, 1954;WICK et al., 1957) and in purified kidney preparations it has been reported to block conversion of glucose-6-phosphate to fructose-6-phosphate, with possible secondary effects on hexokinase .Few studies of the effects of 2-deoxyglucose on cerebral metabolism have been reported. Anaerobic glycolysis of rat cerebral cortex slices is inhibited 50 per cent when incubated with 1 m~-2-deoxyglucose plus 15 mwglucose in vitro, a result comparable to those obtained with rat diaphragm or with tumour tissues under similar conditions, but oxygen uptake by rat cerebral cortex appears much less Hereafter referred to as 2-deoxyglucose or 2-DG. 185 186 DONALD B. TOWER sensitive, concentrations of 2-deoxyglucose up to 60 mM being required to achieve 50 per cent inhibition (WOODWARD and HL?) SON, 1954). In studies on brain hexokinase, SOLS and CRANE (1954) found that 2-deoxyglucose is phosphorylated at a rate comparable to that of glucose but that the phosphate ester formed is not a substrate for either glucose-6-phosphate dehydrogenase or phosphohexoseisomerase.Our interest in the effects of 2-deoxyglucose stem from use of incubated slices of cerebral cortex for investigation of various facets of cortical metabolism. As a whole cell preparation with relatively intact and integrated metabolism, slices offer certain adv...