Therapeutic potential of brain-derived neurotrophic factor (BDNF) and a small molecular mimics of BDNF for traumatic brain injury

Traumatic brain injury (TBI) is a major health problem worldwide. Following primary mechanical insults, a cascade of secondary injuries often leads to further neural tissue loss. Thus far there is no cure to rescue the damaged neural tissue. Current therapeutic strategies primarily target the secondary injuries focusing on neuroprotection and neuroregeneration. The neurotrophin brain-derived neurotrophic factor (BDNF) has significant effect in both aspects, promoting neuronal survival, synaptic plasticity and neurogenesis. Recently, the flavonoid 7,8-dihydroxyflavone (7,8-DHF), a small TrkB agonist that mimics BDNF function, has shown similar effects as BDNF in promoting neuronal survival and regeneration following TBI. Compared to BDNF, 7,8-DHF has a longer half-life and much smaller molecular size, capable of penetrating the blood-brain barrier, which makes it possible for non-invasive clinical application. In this review, we summarize functions of the BDNF/TrkB signaling pathway and studies examining the potential of BDNF and 7,8-DHF as a therapy for TBI.