In vivo study design. Lateral fluid-percussion-induced (FPI) traumatic brain injury (TBI) was performed on day 0. Treatment with vehicle (Vehicle-TBI group, n = 15) or clomipramine (Clomi-TBI group, n = 11) was initiated between 08:00–12:00 at 3 days post-TBI via subcutaneous osmotic minipumps and discontinued between 08:00–12:00 at 14 days by removing the minipumps. Functional outcome was assessed by composite neuroscore and beam-walking tests before TBI (baseline) and at 2, 7, 14 and 28 days post-TBI. Spatial learning and memory were assessed with the Morris water-maze at 21–23 days and 25 days post-TBI. Tail vein blood was collected at 7, 14 and 28 days to assess plasma cytokine levels as monitoring biomarkers. General animal welfare was monitored 3 days before TBI and thereafter, at 1–7, 9, 11, 14, 17 and 21 days post-TBI. At the end of the experiment, rats were perfused for histology (see Figure S1).