Table 1 Summary of dysregulated glial phenotypes and their hypothesised effect on neuronal function.

Increased astrocytic and microglial reactivity associated with enhanced proinflammatory cytokine production [21, 31, 84, 87]

Pro-inflammatory cytokines can induce neuronal apoptosis, alter synaptic function, and facilitate vascular dysfunction [138,139,140,141]

Reduced glucose uptake and cerebral blood flow [36,37,38,39,40]

Reduced energy supply to neurons, which can lead to excitotoxicity-mediated cell death [142]

Glymphatic impairment [60]

Accumulation of metabolic toxins and waste products can impair neuronal function [58, 59]

White matter dysfunction associated with white matter hyperintensities and reduced fractional anisotropy [120, 128, 129]

Reduced speed and quality of signals within networks [143,144,145]

Blood-brain barrier dysfunction and hyperpermeability [28, 105]

Entry of toxins, pathogens and peripheral immune cells into the brain via a leaky blood-brain barrier can damage neuronal networks and dysfunctional efflux via this barrier also impairs the removal of toxins and waste products [103, 117]