Table 1.

Key astrocyte functions.

Function	Description
Synapse Formation and Neuronal Development
Synapse formation	Release of pro-synaptic molecules to increase synapse formation and function as part of the tripartite synapse [2].
Synapse elimination	Mediate synapse elimination through MEGF10 and MERTK pathways [3].
Neuronal growth	Secretion of neurotrophic growth factors (BDNF, NGF, GDNF) [4].
Secretion of extracellular matrix (ECM).	Express a range of proteoglycans essential for CNS extracellular matrix formation and neuronal adhesion molecules (N-cadherin, laminin and neural cell adhesion molecule (NCAM) during development, in health and following injury [5].
CNS Homeostasis
Antioxidant function	Provide antioxidant support to nearby neurons (expanded below).
Glutamate uptake	Express glutamate transporters and play an essential role in CNS glutamate uptake and recycling [6].
Ammonia clearance	Detoxify ammonia by converting it into glutamine, with astrocyte dysfunction being implicated in hepatic encephalopathy [7].
Water homeostasis	Express aquaporin water channels on their basal membrane which are essential for CNS water homeostasis [8].
K+ balance	Elevated K+ following synaptic transmission is cleared by astrocytes; redistributed through astrocyte gap junctions and returned at sites of low K+ concentration via astrocyte Kir 4.1 channels [9].
CNS Metabolism
Provision of metabolic precursors	Astrocytes are the main uptakers of CNS glucose from the blood, which has been proposed to be used to produce lactate for neuronal metabolic function as part of the astrocyte-neuron lactate shuttle [10,11].
CNS glycogen storage	Astrocytes are the predominant glycogen store in the CNS, and astrocyte glycogen is essential in protecting the brain from hypoglycaemia [12]
Vascular Coupling
Vasomodulation and neurovascular modulation	Astrocytes contact the vasculature, and are hypothesised to be responsible for reactive hyperaemia – the process where blood flow in local parts of the brain is coupled to activity [13].
Regulation of blood brain barrier permeability	Astrocyte end-feet are one constituent of the BBB, and astrocyte transporter expression and end-feet anatomy can modulate BBB permeability [14].
Injury Response
Formation of glial scar	Following injury, astrocytes become reactive and proliferate, forming a glial scar to contain inflammatory processes which can be beneficial for recovery [15].
Inflammatory cytokine production and complement activation.	Astrocytes secrete both proinflammatory and anti-inflammatory cytokines and chemokines, including Il-1, IL-6, TNF-alpha and IFN-gamma [16]. They also secrete complement factors C1q and C3, which activates complement and postulated to mediate synapse loss in dementia [17].
Other Functions
Thyroid hormone activation	Uptake inactive T4 hormone from the blood and convert to active T3 [18]. Activated thyroid hormone is essential for myelination and brain development.
Cholesterol synthesis	Astrocytes have a key role in producing cholesterol. This is secreted and delivered to neurons as a complex with apolipoprotein (apo) E and required for neuronal membrane formation and synapse function [19].
Glymphatic flow	Astrocyte pulsatile motion is coupled with water egress through vascular-bound aquaporin channels required for pumping and clearing CNS waste through the glympathic system – the CNS equivalent of the lymphatic network [20]
Circadian rhythm	Astrocyte regulation of extracellular glutamate modulates the oscillatory patterns of neurons in the suprachiasmic nucleus to regulate night-time activity of the mammalian circadian clock [21].