TABLE 1.
Summary of tests for anxiety-like behavior and results from translational TBI studies.
| Behavior test | Injury model | Species and strain | Injury details | Testing details | Effect of TBI | References |
| Open field | Controlled cortical impact | Sprague-Dawley male rats, 90 days old, 300–325 g | Parietal cortex, 6 mm diameter tip, 2.8 mm depth, 4 m/s velocity | Day 8 post-injury | No effect | de la Tremblaye et al., 2021 |
| Sprague-Dawley male rats, 5–6 weeks old | Parietal cortex, 3 mm diameter tip, 2.0 mm depth, 3.5 m/s velocity | Days 1, 7, and 30 post-injury | Reduced time spent in the center on days 7 and 30 (increased anxiety) | Almeida-Suhett et al., 2014 | ||
| C57 mice, male, 14 weeks old | Parietal cortex, 3 mm diameter tip, 2.0 mm depth, 2.5 m/s velocity | Day 67 post-injury | No effect | Islam et al., 2021 | ||
| C57 mice, female, 8–9 weeks old | Parietal cortex, 3 mm diameter tip, 1.5 mm depth, 6 m/s velocity | Days 1, 3, and 5 post-injury | No effect | Ritter et al., 2021 | ||
| C57 mice, 3 months old | Parietal cortex, 3.5 mm diameter tip, 1.5 mm (mild), 2.0 mm (moderate), or 2.5 mm (severe) depth, 5.25 m/s velocity | Day 21 post-injury | No effect | Washington et al., 2012 | ||
| C57 mice, male and female, 9–10 weeks old | Parietal cortex, 3 mm diameter tip, 1.5 mm depth, 4.5 m/s velocity | Days 1, 10, 20 | Reduced distance traveled in the center for mice in the severe group (increased anxiety) | Tucker et al., 2017 | ||
| C57 mice, male, 8–12 weeks old | Parietal cortex, 3 mm diameter tip, 1.0 (mild) or 2.0 (severe) mm depth, 5.0 m/s velocity | Day 7 | No effect | Lee et al., 2019 | ||
| C57 male mice, 6–8 weeks old | Parietal cortex, 3 mm diameter tip, 1.5 mm depth, 4.5 m/s velocity | Weeks 1, 3, 5 and 7 post-injury | Increased time spent in center zone at week 7 (decreased anxiety) | Popovitz et al., 2019 | ||
| Fluid percussion injury | Sprague-Dawley male rats, ∼350 g | 3.25 ATM pressure | Days 29 and 127 post-injury | Reduced time spent in the center (increased anxiety) on Day 29 | Lapinlampi et al., 2020 | |
| Sprague-Dawley male rats, 250–300 g | 2.5–3.0 ATM pressure | Day 35 post-injury | Reduced time spent in the center (increased anxiety) | Das et al., 2019 | ||
| Sprague-Dawley male rats, 279–420 g | 2.19 ATM pressure | Days 7 and 28 post-injury | No effect of injury at Day 7; on Day 28 injured rats spent less time and made fewer entries into the center of the arena (increased anxiety) | Beitchman et al., 2020 | ||
| Wistar rats, male, 175–200 g | >2 ATM pressure | Day 7 post-injury | Reduced time spent in the center (increased anxiety) | Fucich et al., 2019 | ||
| Light-dark box | Controlled cortical impact | C57 mice, male and female, 9–10 weeks old | Parietal cortex, 3 mm diameter tip, 1.5 mm depth, 4.5 m/s velocity | Days 2 and 21 post-injury | Reduced time spent in the dark chamber in “severe” TBI mice (decreased anxiety) | Tucker et al., 2017 |
| C57 mice, male, 8–12 weeks old | Parietal cortex, 3 mm diameter tip, 2.0 mm depth, 3.0 m/s velocity | Day 7 post-injury | No effect | Lee et al., 2019 | ||
| Fluid percussion injury | C57 mice, male, 8–10 weeks old | 1.94 ATM pressure | Day 32 post-injury | No effect | O’Brien et al., 2021 | |
| C57 mice, male, 9 weeks old | 0.68 and 1.36 ATM pressure | 48 h and 14 days post-injury | Decreased time spent in the light chamber (increased anxiety) and reduced number of transitions | Bhowmick et al., 2021 | ||
| Sprague-Dawley rats, male, 200–300 g | 2.0 ATM pressure | 1, 2, 3 and 4 weeks post-injury | Decreased time spent in the light chamber and fewer entries into light conditions (increased anxiety) | Barretto et al., 2021 | ||
| Elevated plus maze | Controlled cortical impact | Sprague-Dawley rats, male, 300–350 g | Parietal cortex, 4 mm diameter tip, 1.5 mm depth, 5 m/s velocity | Days 2, 8, 15, and 29 post-injury | No effect | Tchantchou et al., 2021 |
| Swiss Webster mice, male, 6–8 weeks old | Parietal cortex, 3 mm diameter tip, 1.2 mm depth, 5 m/s velocity | Day 17 post-injury | Decreased entries to open arms (increased anxiety) | Karelina et al., 2021 | ||
| C57 male mice, 6–8 weeks old | Parietal cortex, 3 mm diameter tip, 1.5 mm depth, 4.5 m/s velocity | Weeks 1, 3, 5 and 7 post-injury | Decreased time in the open arms at Week 3 time point (increased anxiety) | Popovitz et al., 2019 | ||
| C57 mice, 3 months old | Parietal cortex, 3.5 mm diameter tip, 1.5 mm (mild), 2.0 mm (moderate), or 2.5 mm (severe) depth, 5.25 m/s velocity | Day 21 post-injury | All injured mice spent more time in the open arms (decreased anxiety) | Washington et al., 2012 | ||
| C57 mice, male, 2–4 months old | Parietal cortex, 3.0 mm diameter tip, 0.6 mm depth, 6 m/s velocity | Day 7 post-injury | No effect | Sierra-Mercado et al., 2015 | ||
| C57 mice, male, 2–3 months old | Parietal cortex, 3.0 mm diameter tip, 0.8 mm depth, 4.5 m/s velocity | Day 28 post-injury | No effect | Watanabe et al., 2013 | ||
| C57 mice, male, 3 months old | Parietal cortex, 3 mm diameter tip, 1.0 mm depth, 3.0 m/s velocity | Days 1 and 2 post-injury | Decreased number of open arm entries and open arm time on both Days 1 and 2 (increased anxiety) | Chauhan et al., 2010 | ||
| Fluid percussion injury | Rats, female, 4 months old | 2.0 ATM pressure | Day 9 post-injury | No effect | Stielper et al., 2021 | |
| Sprague-Dawley male rats, adult | 3.25 ATM pressure | Days 28 and 126 post-injury | On Day 28, injured rats had longer latency to first entry to closed arm (decreased anxiety). On Day 126, injured rats made fewer entries and spent less time in open arms (increased anxiety). | Lapinlampi et al., 2020 | ||
| Wistar male rats, 120 days old, 280–320 g | 1.55 ATM pressure | Day 14 post-injury | Injured rats spent less time in the open arms (increased anxiety) | Dobrachinski et al., 2019 | ||
| C57 mice, male, ∼10 weeks old | 1.0–1.5 ATM pressure | Separate groups of animals tested 1 week or 12 weeks post-injury | Injured mice spent greater time in the open arms 1 week after injury (decreased anxiety). At 12 weeks, injured mice spent less time in the open arms (increased anxiety). | Tan et al., 2020 | ||
| C57 mice, male, 8–10 weeks old | 1.94 ATM pressure | Day 33 post-injury | No effect | O’Brien et al., 2021 | ||
| CHIMERA | C57 mice, male, 8 weeks old | Repeated injury, once a day for 5 days, 0.5 J impact energy | Day 26 post-injury | Increased time spent in open arms (decreased anxiety) | Nolan et al., 2018 | |
| Elevated zero maze | Controlled cortical impact | C57 male mice, 6–8 weeks old | Parietal cortex, 3 mm diameter tip, 1.5 mm depth, 4.5 m/s velocity | Weeks 1, 3, 5, and 7 post-injury | Decreased time in open quadrants at week 1 (increased anxiety), increased time in open quadrants at week 5 (decreased anxiety) | Popovitz et al., 2019 |
| C57 mice, male, 14 weeks old | Parietal cortex, 3 mm diameter tip, 2.0 mm depth, 2.5 m/s velocity | Day 31 post-injury | Injured mice spent more time in the open quadrants (decreased anxiety) | Islam et al., 2021 | ||
| C57 mice, male and female, 9–10 weeks old | Parietal cortex, 3 mm diameter tip, 1.5 mm depth, 4.5 m/s velocity | Days 2 and 21 post-injury | Mice with severe injury spent less time in the darker quadrants (decreased anxiety) | Tucker et al., 2017 | ||
| C57 mice, male, 8 weeks old | Parietal cortex, 3 mm diameter tip, 1.5 mm depth, 5.0 m/s velocity | Days 6 and 14 post-injury | Time spent in the open quadrant per visit was decreased on day 14 (increased anxiety) | Tchantchou et al., 2014 | ||
| Fluid percussion injury | C57 mice, male and female, 8–10 weeks old | Pressure not given | Day 3 post-injury | Injured mice show preference for closed quadrants (increased anxiety) | Tapp et al., 2020 |