Post-Injury Treatment of 7,8-Dihydroxyflavone Promotes Neurogenesis in the Hippocampus of the Adult Mouse

Abstract

Traumatic brain injury (TBI) at the moderate level of impact induces massive cell death and results in extensive dendrite degeneration in the brain, leading to persistent cognitive, sensory, and motor dysfunction. Our previous reports have shown that adult-born immature granular neurons in the dentate gyrus are the most vulnerable cell type in the hippocampus after receiving a moderate TBI with a controlled cortical impact (CCI) device. There is no effective approach to prevent immature neuron death or degeneration following TBI. Our recent study found that pretreatment of 7,8-dihydroxyflavone (DHF), a small molecule imitating brain-derived neurotrophic factor, protected immature neurons in the hippocampus from death following TBI. In the present study, we systemically treated moderate CCI-TBI mice or sham surgery mice with DHF once a day for 2 weeks via intraperitoneal injection, and then assessed the immature neurons in the hippocampus the 2nd day after the last DHF injection. We found that post-injury treatment of DHF for 2 weeks not only increased the number of adult-born immature neurons in the hippocampus, but also promoted their dendrite arborization in the injured brain following TBI. Thus, DHF may be a promising compound that can promote neurogenesis and enhance immature neuron development following TBI.