Fig. 2: Pan-adrenergic inhibition improves behavioral outcomes of KA-induced chronic epilepsy. | Nature Communications

Fig. 2: Pan-adrenergic inhibition improves behavioral outcomes of KA-induced chronic epilepsy.

From: Enhancing glymphatic fluid transport by pan-adrenergic inhibition suppresses epileptogenesis in male mice

Fig. 2

A Timeline of the experimental design. Five minutes after intrahippocampal KA infusion, mice were randomly divided into two groups that received daily injections of either PPA or vehicle for three consecutive days. After 3–4 weeks, cortical EEG electrodes were implanted in a subgroup of mice and EEG recordings obtained one week later. In parallel, we measured open-field and Rota-rod behavioral scores in a separate group of mice. B Seizure event plots show each convulsive seizure (red dot) onset time for individual mice in four-day recordings from the KA (left) and PPA-treated KA (right) groups. Heatmap (below) indicates the frequency of seizure onsets per mouse per four-hour recording in each group. C Kaplan–Meier survival curve of Sham, KA-Veh and KA-PPA (5 min) groups after KA infusion (n = 12 each, Sham vs KA-Veh *P = 0.039, KA-Veh vs KA-PPA **P = 0.003, Log-rank test). D The numbers of seizures in 4-day recordings, duration of spontaneous seizures, maximum Racine scale in four days, and number of seizure-free days contrasted between KA-Veh and KA-PPA mice. KA-Veh (n = 6) versus KA-PPA (n = 7). Seizure numbers, *P = 0.044 (two-tailed Mann–Whitney test); seizure duration, *P = 0.031 (unpaired two-tailed t-test); maximal Racine scale, *P = 0.048 (two-tailed Mann–Whitney test) and seizure-free days, P = 0.237 (unpaired two-tailed t-test). E The representative traces of motion trails in the open-field test among Sham, KA-Veh and KA-PPA groups (left). The comparisons of total distances traveled are presented on the right. (one-way ANOVA, Tukey’s multiple comparisons test, Sham (n = 5) vs KA-Veh (n = 5) **P = 0.006, KA-Veh (n = 5) vs KA-PPA (n = 6) *P = 0.013). F Motor coordination and motor learning by the Rota-Rod test showing partial recovery with PPA treatment. Comparison of the latency to fall among Sham, KA-Veh and KA-PPA groups (two-way ANOVA, Tukey’s multiple comparisons test, Sham (n = 7) vs KA-Veh (n = 8), ***P < 0.001, **P = 0.005; KA-Veh (n = 8) vs KA-PPA (n = 8) #P < 0.05). Data are presented as mean ± SEM.

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