Astrocyte innate immune activation and injury amplification following experimental focal cerebral ischemia

Astrocytes are a distinct population of glial cells responsible for many homeostatic functions in normal neural architecture. In the healthy brain, astrocyte functions range from maintenance of the blood brain barrier to modulation of synaptic transmission and neuronal plasticity to glial scar formation post-ischemic injury. In humans, this group of cells exhibits far greater heterogeneity than previously thought-with distinct subpopulations that likely carry out specialized functions. Following ischemic injury, astrocytes take on a distinct phenotype-known as the reactive astrocyte. This phenotype is responsible for both the propagation and amelioration of neuronal injury during ischemia. Following ischemia, astrocytes undergo temporal and spatialdependent changes in morphology, gene expression, hypertrophy and hyperplasia as a result of signaling within the local microenvironment of the penumbra compared to the core infarct. This elicits a cascade of downstream effects, including inflammation and activation of the innate immune system, which both propagates and ameliorates local injury within the brain parenchyma. This review will focus upon the double-edged sword-that are astrocytes and the innate immune system. We will discuss the role that astrocytes and the innate immune system play in amplifying secondary brain injury, as well as attenuating ischemic damage. Specifically, we will focus on molecular signaling and processes that could be targeted as potential therapeutic interventions.

Automated summary

Astrocytes are glial cells that play important roles in the healthy brain, including maintaining the blood brain barrier, modulating synaptic transmission and neuronal plasticity, and forming glial scars following ischemic injury. Following ischemia, astrocytes undergo specific changes in phenotype and gene expression, contributing to both the propagation and amelioration of neuronal injury. This review focuses on the dual role of astrocytes and the innate immune system in amplifying secondary brain injury and attenuating ischemic damage, discussing potential molecular signaling and processes that could be targeted for therapeutic interventions.