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. 2011 Mar 24;8(2):304–315. doi: 10.1007/s13311-011-0039-z

FIG. 3.

FIG. 3

Schematic representation of the treatment protocols in chronic epileptic mice. Panel (a) depicts the treatment protocol used in 5 randomly chosen epileptic mice: after establishing the baseline of spontaneous epileptic activity, the mice were treated intraperitoneally with a single dose of 50 mg/kg phenytoin. Then they underwent a 3-day wash-out period before entering protocol (b) (200 mg/kg VX-765). Panel (b) depicts the treatment protocol of 21 epileptic mice with VX-765: 3 days of electroencephalographic (EEG) baseline recording was done, and on day 4, the vehicle of VX-765 was injected intraperitoneally twice (at 9:00 AM and 4:00 PM), and on the following day, the epileptic mice received VX-765 twice a day (at 9:00 AM and 4:00 PM) for 4 consecutive days, and the EEG recording was done for 2 h after each drug administration. The last drug administration was followed by a 3-day wash-out period, and each day EEG was recorded (at 9:00 AM to 11:00 AM) to evaluate the time required by each epileptic mouse to recover its pre-injection baseline activity after drug withdrawal. Mice injected with VX-765 were killed for histological analysis (i.e., 5 mice at the time of maximal drug effect and 4 mice after drug wash-out). Panel (c) depicts the treatment protocol with dexamethasone: 6 epileptic mice at the end of treatment with 50 mg/kg VX-765, according to protocol (b), including the 3-day wash-out period were recorded by EEG continuously (between 9:00 AM and 5:00 PM) for 3 additional days (days 1–3) to monitor if the baseline epileptic activity had resumed and was stable. Then the vehicle was subcutaneously injected on day 4 (at 9:00 AM and 4:00 PM); on day 5, the baseline was again recorded (between 9:00 AM and 11:00 AM), followed by a subcutaneous injection of dexamethasone in alcohol formulation (3 mg/kg). An EEG recording was continued for an additional 6 h (i.e., until 5:00 PM). This procedure was repeated for 3 consecutive days. A 3-day wash-out period followed the last dexamethasone dose. d = day; DEX = dexamethasone.