Fig. 8
Telemetric measurements of ICP in freely moving awake rats before and during treatment with AZE. Top panels represent the recovery period after implantation of telemetric device and show daily fluctuations in ICP (A), MAP (B) and heart rate (C). D The average ICP over 3 days (72 h) before initiation of treatment (ICPCTRL = 3.9 ± 0.7 mmHg, ICPAZE = 3.7 ± 1.1 mmHg, n = 4 in each, P = 0.8, unpaired t-test). The % change in ICP, normalized to the average 24 h ICP (baseline) before treatment initiation, is shown in E for 1× daily p.o. delivery of 100 mg kg−1 AZE or control solution. The difference between the lowest 1 h average ICP value (within the first 7 h after AZE or control solution injection) and the baseline ICP is shown in F (n = 4 in each group, P < 0.001, unpaired t-test). The ICP fluctuations over the 24 h period after drug administration are represented in G (n = 4 in each group, 2way ANOVA with Bonferroni’s post-hoc analysis), where an average ICP for each 2 h period was calculated for controls and AZE treated rats across the six treatment days. 2–3 h after p.o. drug administration an IRDye 800 CW carboxylate dye was injected intraventricularly, and the dye flow (H) and rate (I, nCTRL = 6, nAZE = 5, P < 0.01, unpaired t-test) was used as a proxy to assess the CSF secretion rate. The maximum effect of the 3× day treatment with 100 mg kg−1 AZE or control solution for 5 days is shown in panel J (n = 4 in each group, P < 0.05, unpaired t-test). The ΔICP was calculated as difference between the baseline ICP and minimum 1 h average ICP during the 7 h after each (of 14) AZE or control solution p.o. delivery. In K, ICP fluctuations during the 3× day treatment, normalized to baseline ICP are shown. The average ICP at 6, 13 and 20 o’clock (the hour before p.o. treatment administration) was calculated for the baseline period, and compared to average ICP at the same time points during 3× day treatment with 100 mg kg−1 AZE (L, n = 12, P < 0.01, paired t-test) or control solution (M, n = 12, P = 0.7, paired t-test). ICP – intracranial pressure, MAP – mean arterial pressure, HR – heart rate, CTRL – control, AZE – acetazolamide, BSL – baseline, a.u. – arbitrary units. Data are shown as mean ± SD. *; P < 0.05, **; P < 0.01, ***; P < 0.001, ns; not significant.