Effects of Short Chain Fatty Acids on the Perfused Cat Brain

Abstract

This study was aimed to elucidate the effects of short chain fatty acids such as N-sodium butyric acid, N-sodium valeric acid, N sodium caproic acid and gamma-hydroxybutyrate (OBA), on the cerebral blood flow, oxygen consumption, glucose uptake, lactic acid output and EEG of the perfused brain. The brain perfusion was conducted by a modified method of Geiger and Magnes with non-anesthetized cats made immobile with d-tubocurarine. During the brain perfusion, 1 ml of artificial blood containing the aqueous solution (pH 7.4) of 0.1 or 1.0 m mole each of N-sodium butyric acid, N-sodium valeric acid, N-sodium caproic acid, or 0.09 m mole of OBA was injected intracarotidly. The results are briefly summarized as follows.
1) In the rapid administration of these short chain fatty acids EEG in all the cases tended to show slow waves 30-40 seconds after the start of the injection, indicating a marked inhibitory effect on the EEG. As for the degree of this inhibition it was most marked with N-caproic acid followed by N-valeric acid, OBA and N-butyric acid in that descending order.
Among them, especially in the cases administered with 1.0 m mole of N-caproic acid and N-valeric acid, there appeared slow wave followed by its flattening on EEG, indicating an irreversible strong inhibitory effect on EEG, and also a marked inhibitory effect on the vital signs of the cat.
In the cases given 0.1 m mole of N-butyric acid or N-valeric acid, slow wave on EEG was transient, lasting cn for 20-30 seconds, which was reversible without flattening and tended to recover rapidly. The tendency was especially marked with the administration of 0.1 m mole of N-butyric acid.
In the cases administered with 0.09 m mole of OBA, marked slow waves lasted for a long time, but 10 minutes after the commencement of the administration, the fast wave component increased and there was observed a recovery of the response to sound stimuli.
2) In the cases administered with 0.1 m mole of N-butyric acid, N-valeric acid, N-caproic acid and with 0.09 m mole of OBA, every case showed an increase in the cerebral blood flow along with the appearance of slow wave on the EEG with the time difference of about 10 seconds. Especially marked was the accelerating effect of N-butyric acid at the dose of 0.1 m mole on the cerebral blood flow, and it lasted for a fairly long time and this increased blood flow persisted even when the slow wave had disappeared and the EEG had returned to the normal level. On the contrary, in the cases administered with a high dose (1.0 m mole) of N-caproic acid or N-valeric acid, the enhancing effect on the cerebral blood flow was extremely slight, indicating that the inhibitory effect of these short chain fatty acids on the central nervous system does not necessarily coincide with their accelerating effect on the cerebral blood flow.
3) All these short chain fatty acids showed an accelerating effect on the glucose uptake in the brain, and this effect was most marked in the case administered with 0.1 m mole of N-butyric acid.
As for the other fatty acids they showed only 1/2-1/3 the accelerating effect of N-butyric acid, of them OBA showing the lowest effect.
4) The rapid administration of these short chain fatty acids hardly has any effect on the oxygen consumption and the lactic acid output in the perfused brain.
In other words, although these short chain fatty acids possess an inhibitory effect on the EEG of the neocortex of the perfused cat brain, they act acceleratingly on the glucose uptake. This fact seems to indicate that the mechanism of the inhibitory action on the central nervous system by these short chain fatty acids differs from that of other hypnotics and anesthetics.