Daytime modulation of cortical spreading depression according to blood glucose levels

The aim of this study was to investigate the effects of daytime and blood glucose levels on the propagation of cortical spreading depression (SD). Thirty-nine male Wistar rats were used. Animals were housed 5 per cage with a 12-h, light-dark cycle (lights on at 0600 h). Food and water were available ad libitum, and animals were fasted the night before the experiments. Cortical SD was recorded continuously for 3 h using Ag-AgCl agar-Ringer electrodes placed on the parietal cortex. Every 20 min, SD was elicited by 2% KCl stimulation of the frontal cortex for 1 min. After 1 h of SD-recording, blood glucose levels were measured, and animals were injected intravenously either with glucose (40% solution, 1 mL), insulin (0.3 U/100 g of body weight), or mannitol (20% solution, 1 mL). In the middle of the light period, which corresponds to zeitgeber time (ZT)5, 8 animals received glucose, 7 received insulin, and 6 received mannitol. In another experimental set, glucose or insulin was administered at ZT12 (at the end of the light period); 12 rats received glucose, and 6 received insulin. All the animals that received glucose were hyperglycaemic (P < 0.01), and the hyperglycaemia was less pronounced in the ZT12 group (P < 0.05; Student's t-test). Insulin induced acute hypoglycaemia in animals of both groups (ZT5, P < 0.02; ZT12, P < 0.05; Student's t-test). Glucose injection at ZT5 reduced SD, whereas the insulin ZT5 group showed increased SD propagation (ANOVA, P < 0.05 and 0.01, respectively). Neither glucose nor insulin injection changed SD velocity at ZT12. We concluded that blood glucose levels change the velocity of SD propagation and that these effects are influenced by the daytime. Dark periods seemed to produce a resistance to cortical SD propagation.

Research highlights▶ Cortical spreading depression (SD) propagation changes according to daytime. ▶ In the middle of LD cycle glycaemia induces differential changes on SD. ▶ In the end of light phase brain ability to propagate SD is reduced.