Effects of Various Cerebral Metabolic Activators on the Glucose Metabolism of Brain

Recently there have been developed various activators of the brain metabolism as therapeutic agents for the treatment of functional deficiency of the brain in residual lesions due to traumatic and vascular disturbances of the head and in geriatric mental disorders. I have investigated the effects of these agents on brain glucose metabolism, cerebral blood flow, systemic blood pressure, EEG, cerebral oxygen consumption, cerebral carbon dioxide production, cerebral lactic acid release, and cerebral glucose uptake by means of the brain perfusion and in vivo chronic administration of these agents. The agents studied were four in all; namely, 1) 5'Cytidine monophosphate-2 Na, 2) CDP-choline, 3) Pyrithioxin, and 4) Meclophenoxate. For the brain perfusion I used the method which has advantage of studying the direct effect of the agents on the brain tissue only without involvement in the metabolism of organs other than brain, in which the brain circulation is shunted from the systemic circulation and artificial blood of known composition is perfused. Furthermore, since the constant radioactivity through the experiments of 〔U-(14)C〕 glucose in the blood always maintained, it is easy to know its involvement in the brain metabolism. The results may briefly be summarized as follows. 1) When the brain perfusion is done with the blood containing Cytidine monophosphate, the incorporation of the blood 〔U-(14)C〕 glucose into the cerebral metabolites is enhanced as comp-ared to the perfusion of blood without cytidine monophosphate. 2) In the experiments where Pyrithioxin or Meclophenoxate is acutely administered, there can be observed no effect on the metabolic rate of the brain nor on the incorporation of blood 〔U-(14)C〕 glucose into cerebral glucose related substances. 3) There can be seen no effect of chronic administration of Pyrithioxin or Meclophenoxate on the 〔U-(14)C〕 glucose metabolism of mouse brain. 4) When the brain is perfused with the blood containing CDP-choline, the rate of incorporation of 〔U-(14)C〕 glucose (RSA) into the cerebral glucose metabolites is enhanced and it acts as to activate the brain glucose metabolism, when compared with the standard perfusion corresponding to the EEG level. 5) To the rate of cerebral blood flow, CDP-choline acts as to increase it temporarily, while Pyrithioxin or Meclophenoxate has no effect at all. 6) The systemic blood pressure is raised temporarily by Pyrithioxin or Meclophenoxate, while it is decreased temporarily by CDP-choline