(A) Schematic of experimental design. (B) Model figure. Daily cycles in behavior and physiology (black line) are dampened in stroke (dotted red line), leading to decreased glymphatic function and cytokine accumulation. Chronotherapy (KL001, green; active-phase restricted feeding, blue) can reinforce 24-hour behavior and physiology (purple line). Glymphatic function is increased, cytokine burden is decreased, and stroke recovery is improved. An important note is that although chronotherapy may reinforce timing, the change in endogenous rhythms may be intervention and disease specific. (C) Violin plot of all individual brain cytokine concentrations normalized to the peak value with and without KL001. Box plot of normalized cytokine concentration by mouse. Normalized group mean of cytokine concentrations. Darker gray indicates increased concentration, green border indicates decreases with KL001, and red border indicates increases with KL001. Values to the right are all P values under 0.2 for group comparisons. (D) Same as in C, but with active-phase time-restricted feeding. (E) Same as in C and D, but measured in blood after KL001 chronotherapy. (F) Same as in E, but measured in blood after active-phase time-restricted feeding chronotherapy. For violin plots, vehicle/ad libitum (gray), KL001 (green), and active-phase time-restricted feeding (blue). Width reflects concentration of data, dotted lines indicate upper and lower quartile limits, solid black lines indicate median, and individual points represent individual cytokine values. For box plots, vehicle/ad libitum (gray), KL001 (green), and active-phase time-restricted feeding (blue). Minimum and maximum values are shown, center lines indicate the medians, and quartiles are shown by box-and-whisker plots, with individual mice shown as colored dots. *P < 0.05, **P < 0.01, ***P < 0.001. An unpaired t test, an unpaired t test with Welch’s correction, or a Mann-Whitney test were used for statistical tests across panels. All statistics are shown in Supplemental Table 1.