Neuregulin-1 (NRG1) is a growth factor that belongs to a family of polypeptide growth factors encoded by four neuregulin genes. NRG1 signals are transduced through the ErbB family of receptor protein tyrosine kinases, in which NRG1 binding results in phosphorylation and dimerization of these receptors, leading to activation of downstream pathways. NRG1/erbB signaling is involved in cellular processes including cell survival, proliferation, migration, and differentiation. In the CNS, NRG1/ErbB4 signaling also affects dendritic spine maturation and the formation of inhibitory synapses. Neuregulin-1/ErbB signaling has been shown to have beneficial effects on many of the different types of cells in the brain, including neurons, astrocytes, oligodendrocytes, oligodendrocyte precursor cells, endothelial cells, and microglia. Many of these actions may have neuroprotective potential in the setting of traumatic brain injury, and will be further discussed in this chapter.
Traumatic brain injury (TBI) is a significant public health problem, affecting individuals of all ages daily. Survivors are often left with motor and cognitive deficits, ranging from mild to devastating. Because there is no definitive treatment beyond supportive care in the acute postinjury period, there is much focus on searching for neuroprotective agents that will attenuate the pathological events that arise after the injury. The process is challenging because of the heterogeneity of TBI. An attempt to classify TBI highlights the diverse array of injuries—for example, focal or diffuse, mild or severe, presence or absence of hemorrhage, a concussion or a contusion, or a single hit or repeated hits. It is likely that no single agent will be efficacious for the different types of TBI, and it is necessary to understand the pathophysiology of the various injuries and investigate appropriate therapies for each type of injury. Here the term “traumatic brain injury” is used as a general term, with the understanding that it is a simplification of the complex nature of TBI.
In recent years, there has been an increasing amount of research and interest in NRG1 an endogenous growth factor with multiple functions in the central nervous system (CNS), and now in clinical trials for the treatment of patients with chronic heart failure. The actions of NRG1 intersect with many cellular pathways, thus it may have applicability to many of the pathological processes in TBI. In this chapter, we will review pathophysiological processes after TBI that intersect with NRG1/ErbB signaling as well as experimental data in models of brain trauma suggesting that NRG1 may be neuroprotective. Because some of the brain injury pathways in TBI are similar to those in ischemic brain injury (Bramlett and Dietrich, 2004), literature on the effects of NRG1 in models of ischemic stroke will also be discussed.
© 2015 by Taylor & Francis Group, LLC.