Modulation of neurotrophic factors in the treatment of dementia, stroke and TBI: Effects of Cerebrolysin.

Neurotrophic factors (NTFs) are involved in the pathophysiology of neurological disorders such as dementia, stroke and traumatic brain injury (TBI), and constitute molecular targets of high interest for the therapy of these pathologies. In this review we provide an overview of current knowledge of the definition, discovery and mode of action of five NTFs, nerve growth factor, insulin-like growth factor 1, brain derived NTF, vascular endothelial growth factor and tumor necrosis factor alpha; as well as on their contribution to brain pathology and potential therapeutic use in dementia, stroke and TBI. Within the concept of NTFs in the treatment of these pathologies, we also review the neuropeptide preparation Cerebrolysin, which has been shown to resemble the activities of NTFs and to modulate the expression level of endogenous NTFs. Cerebrolysin has demonstrated beneficial treatment capabilities in vitro and in clinical studies, which are discussed within the context of the biochemistry of NTFs. The review focuses on the interactions of different NTFs, rather than addressing a single NTF, by outlining their signaling network and by reviewing their effect on clinical outcome in prevalent brain pathologies. The effects of the interactions of these NTFs and Cerebrolysin on neuroplasticity, neurogenesis, angiogenesis and inflammation, and their relevance for the treatment of dementia, stroke and TBI are summarized.