PROJECT: JTC2016: REACT NSCs

Traumatic brain injury (TBI) is becoming a “silent epidemic” worldwide. In Europe, almost 8 million people have significant disabilities due to TBI and the economic cost has been estimated in EUR 100 billion. TBI survivors often develop long lasting neurological symptoms such as decision-making and memory deficits, depression or aggressive behavior, negatively impacting on their quality of life. Several of the important brain functions affected by TBI depend on the hippocampus, which is highly vulnerable to injury. Even when not directly mechanically affected, the hippocampus undergoes atrophy and synaptic alterations. In addition, adult hippocampal neurogenesis (AHN), the process of generating new neurons from neural stem cells (NSCs) located in the dentate gyrus (DG) is affected by TBI. We hypothesize that TBI induces long-term changes in NSCs and newborn neurons, drastically altering the process of neurogenesis and thereby impairing hippocampal circuitry and function. We propose NSCs and AHN should be considered a novel target for developing innovative strategic therapies against brain damage. AHN is highly sensitive to changes in neuronal activity and impairment or alterations of AHN may account for some of the symptoms associated with TBI, such as memory, learning, and anxiety deficits, as these are hippocampal functions in which AHN participates. We have shown that NSCs modify their behavior readily in response to neuronal damage and changes in neuronal activity. Depen