Enhanced Dentate Neurogenesis after Brain Injury Undermines Long-Term Neurogenic Potential and Promotes Seizure Susceptibility

Hippocampal dentate gyrus is a focus of enhanced neurogenesis and excitability after traumatic brain injury. Increased neurogenesis has been proposed to aid repair of the injured network. Our data show that an early increase in neurogenesis after fluid percussion concussive brain injury is transient and is followed by a persistent decrease compared with age-matched controls. Post-injury changes in neurogenesis paralleled changes in neural precursor cell proliferation and resulted in a long-term decline in neurogenic capacity. Targeted pharmacology to restore post-injury neurogenesis to control levels reversed the long-term decline in neurogenic capacity. Limiting post-injury neurogenesis reduced early increases in dentate excitability and seizure susceptibility. Our results challenge the assumption that increased neurogenesis after brain injury is beneficial and show that early post-traumatic increases in neurogenesis adversely affect long-term outcomes by exhausting neurogenic potential and enhancing epileptogenesis. Treatments aimed at limiting excessive neurogenesis can potentially restore neuroproliferative capacity and limit epilepsy after brain injury. •Increase in neurogenesis after TBI is transient and leads to long-term decline•Altered neural precursor proliferation underlies post-TBI changes in neurogenesis•Brief antagonism of VEGFR2 restores post-injury neurogenesis to control levels•Limiting neurogenesis improves excitability and seizure susceptibility after TBI The authors challenge the prevailing assumption that increases in neurogenesis after brain injury are beneficial. They demonstrate that excess post-injury neurogenesis exhausts dentate neurogenic potential and undermines long-term neurogenesis. Treatments suppressing VEGFR2 signaling reduce neurogenesis after injury, reverse ensuing decline in neuroproliferation, and decrease excitability and seizure susceptibility. Thus, limiting excessive neurogenesis could reduce adverse neurological outcomes after brain injury.