Astrocytic-neuronal crosstalk: Implications for neuroprotection from brain injury

► Astrocytic-neuronal interactions as neuroprotective strategy against brain injury. ► Astrocytic support of neurons for brain protection. ► Neuroprotective compounds aimed at manipulating astrocytes for neuronal protection. The older neurocentric view of the central nervous system (CNS) has changed radically with the growing understanding of the many essential functions of astrocytes. Advances in our understanding of astrocytes include new observations about their structure, organization, function and supportive actions to other cells. Although the contribution of astrocytes to the process of brain injury has not been clearly defined, it is thought that their ability to provide support to neurons after cerebral damage is critical. Astrocytes play a fundamental role in the pathogenesis of brain injury-associated neuronal death, and this secondary injury is primarily a consequence of the failure of astrocytes to support the essential metabolic needs of neurons. These needs include K + buffering, glutamate clearance, brain antioxidant defense, close metabolic coupling with neurons, and the modulation of neuronal excitability. In this review, we will focus on astrocytic activities that can both protect and endanger neurons, and discuss how manipulating these functions provides a novel and important strategy to enhance neuronal survival and improve the outcome following brain injury.