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

Abstract

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.

Nelumbo nucifera leaves extract ameliorated scopolamine‐induced cognition impairment via enhanced adult hippocampus neurogenesis

“…35 Upon binding to their receptors, neurotrophic factors, such as BDNF, nerve growth factor-activated downstream targets to trigger neuron differentiation, neural proliferation, and synapse formation. 28,36 BDNF abundantly expressed in the hippocampus and front cortex plays a pivotal role in memory and learning. 28 BDNF interacted with TrkB, promoted its autophosphorylation, and activated three major pathways: (1) phosphoinositide-3 kinase (PI-3 K)/Akt, (2) Ras/ raf/mitogen-activated protein kinase (MAPK) pathways, and (3) CREB protein.…”

Effect of Hyperbaric Oxygen Intervention on Oxidative Stress and Expression of Nerve Growth Factor in Patients with Craniocerebral Injury

“…Nonetheless, numerous studies on NGF in craniocerebral trauma have demonstrated that administration via different routes produces curative effects without obvious adverse effects. 18 It is hypothesized that the administration of NGF through multiple routes and the use of medications to temporarily access the blood-brain barrier following cerebral trauma can ensure the maintenance of a high level of NGF in damaged brain tissue, thus exerting the neuroprotective effect of NGF. In this study, following HBO therapy, there was an improvement in the condition, and the NGF content saw a more significant increase.…”

Impact of subthalamic nucleus deep brain stimulation at different frequencies on neurogenesis in a rat model of Parkinson's disease

“…These cells transform into interneurons and radially migrate to the olfactory bulb (OB) by the rostral migratory stream (RMS) and differentiate into olfactory granule cells (GCs) and periglomerular cells, which integrate into the neuronal circuitry [ 4 , 5 ]. However, it is generally accepted that the proliferation and differentiation of NSCs are influenced by changes of structures in many brain disorders, and new neurons can migrate to impaired regions to facilitate the restoration of neural function, thereby maintaining brain homeostasis [ 6 ].…”