Victims of mild traumatic brain injury (mTBI) do not show clear morphological brain defects, but frequently suffer from long-lasting cognitive deficits, emotional difficulties and behavioral disturbances. In the present study, we investigated the effects of experimental mTBI in mice on cognition, spatial and non-spatial tasks, and depressive-like behavior in mice. Experimental brain injury was induced using a concussive head trauma, which creates the TBI by a weight-drop device. Different groups of mice were tested at 7, 30, 60, and 90 days post-injury for cognitive function (the swim T-maze and the passive avoidance test) and for depression-like behavior (the forced swimming test). These tests have been used infrequently in the past in mTBI research. Significant differences were observed between the injured mice compared to the controls in both the swim T-maze (day 30: p < 0.001) and passive avoidance (day 30: p < 0.05) tests. In addition, a significant difference was detected in the forced swimming test between the injured mice and the controls (day 7: p < 0.05; day 90: p < 0.01), which showed a depressive- like state in the injured animals beginning 7 days post-injury. These results demonstrate that persistent deficits in these tests of cognitive learning abilities and emergence of depressive-like behavior in injured mice are similar to those reported in human post-concussion syndrome.

Victims of minor traumatic brain injury (mTBI), who show no clear morphological brain defects, frequently manifest cognitive, behavioral and emotional difficulties that can be long-lasting. In this paper we present a modified weight drop model used to deliver a closed head minimal traumatic brain injury to mice, which closely mimics real-life injuries and the symptoms observed in mTBI patients. Our choice of impact force does not produce structural damage to the brain and its surrounding tissue (as examined by MRI), any skull fracture, no edema and no evident damage to the blood-brain barrier (BBB). Moreover, our mTBI mice show no abnormal behavior on recovering from the weight drop, or any change in other brain functions such as reflexes, balance, exploration, strength, locomotor activity and swim speed. Since our mTBI model does not produce neurological, motor or sensory damage to the mice, it allows the direct evaluation of mTBI sequelae on the mice behavior and cognitive abilities. Using a variety of cognitive and behavioral tests (Morris water maze, staircase test, passive avoidance test, water T-maze, hot palate, elevated plus maze and forced swimming test) we assessed the short- and long-term sequelae induced by our model. Our results indicate that our closed head mTBI cause profound and long-lasting, irreversible learning and memory impairments, accompanied by a depressive-like behavior in mice that are evident even 90 days post injury. Our results indicate that the closed head mTBI model presented here may be useful in the development of novel therapeutic approaches, such as neuroprotective agents, for mTBI.

Background: Data on the age at first arrhythmic event (AE) in Brugada syndrome are from limited patient cohorts. The aim of this study is 2-fold: (1) to define the age at first AE in a large cohort of patients with Brugada syndrome, and (2) to assess the influence of the mode of AE documentation, sex, and ethnicity on the age at first AE. Methods and Results: A survey of 23 centers from 10 Western and 4 Asian countries gathered data from 678 patients with Brugada syndrome (91.3% men) with first AE documented at time of aborted cardiac arrest (group A, n=426) or after prophylactic implantable cardioverter–defibrillator implantation (group B, n=252). The vast majority (94.2%) of the patients were 16 to 70 years old at the time of AE, whereas pediatric (70 years) comprised 4.3% and 1.5%, respectively. Peak AE rate occurred between 38 and 48 years (mean, 41.9±14.8; range, 0.27–84 years). Group A patients were younger than in Group B by a mean of 6.7 years (46.1±13.2 versus 39.4±15.0 years; P <0.001). In adult patients (≥16 years), women experienced AE 6.5 years later than men ( P =0.003). Whites and Asians exhibited their AE at the same median age (43 years). Conclusions: SABRUS (Survey on Arrhythmic Events in Brugada Syndrome) presents the first analysis on the age distribution of AE in Brugada syndrome, suggesting 2 age cutoffs (16 and 70 years) that might be important for decision-making. It also allows gaining insights on the influence of mode of arrhythmia documentation, patient sex, and ethnic origin on the age at AE.