Chapter 18 - Angiopoietin-1/Tie-2 signaling in traumatic brain injury

Abstract

Traumatic brain injury (TBI) causes severe pathological changes, including neuronal dysfunction and disruption of the blood-brain barrier (BBB). Therefore, treatment of these conditions is a therapeutic strategy for TBI. Angiopoietin-1 (Ang-1) is an angiogenetic glycoprotein that promotes neurogenesis and angiogenesis via activation of Tie-2, a tyrosine kinase receptor. In the brain, Ang-1 is expressed in astrocytes, pericytes, and brain microvascular endothelial cells (BMECs), while Tie-2 is expressed in BMECs and neuronal cells. In some TBI patients, the expression levels of Ang-1 are increased and are associated with good outcome after TBI. In TBI animal models, Ang-1 upregulation and exogenous Ang-1 reduce neuronal apoptosis and promote neurogenesis via phosphorylation of Tie-2. Furthermore, the TBI-induced BBB disruption is alleviated by activation of the Ang-1/Tie-2 signaling pathway. Together, these findings suggest that Ang-1/Tie-2 signaling is neuroprotective against TBI and that drugs that activate this pathway may have therapeutic potential for TBI.