Neurotrophic Factors: Pathophysiology and Therapeutic Applications in Traumatic Brain Injury

Neurotrophic factors (NTFs) are endogenous molecules that play a crucial role in the maintenance, survival and differentiation of various neuronal populations within the developing and adult brain. In vitro and in vivo studies have shown that NTFs can attenuate neuronal injury initiated by cascades that are activated by traumatic brain injury (TBI) including excitotoxic damage, ischemia, and apoptosis. NTFs may also play a role in repair-regeneration processes such as axonal regeneration, neuronal plasticity and neurogenesis that could be critical for recovery after TBI. Nerve growth factor (NGF), insulin like growth factor I (IGF-I) and basic fibroblast growth factor (bFGF) and glial cell-derived neurotrophic factor (GDNF) have been shown to be effective in reducing neurobehavioral dysfunction and/or histopathological damage in experimental models of TBI. NTFs appear to be promising therapeutic tools for TBI, although more studies are necessary to elucidate their potential application and to test delivery systems that allow local, regulated supply to specific populations of neurons. This article provides an overview of the pathophysiology and potential therapeutic application of neurotrophic factors in TBI.