Astrogliosis - Neurological Pathologies

Neurological Pathologies

Loss or disturbance of functions normally performed by astrocytes or reactive astrocytes during the process of reactive astrogliosis has the potential to underlie neural dysfunction and pathology in various conditions including trauma, stroke, multiple sclerosis, and others. Some of the examples are as follows:

• Autoimmune destruction of astrocyte endfeet that contact and envelop blood vessels is associated with CNS inflammation and a form of multiple sclerosis
• Rasmussen’s syndrome autoantibody destruction of astrocytes causes seizures
• In Alexander's disease, a dominant, gain-of-function mutation of the gene encoding GFAP is associated with macro-encephalopathy, seizures, psychomotor disturbances, and premature death.
• In a familial form of amyotropic lateral sclerosis (ALS), a dominant gain-of-function mutation of the gene encoding superoxide dismutase (SOD) leads to production of reactive astrocytes of molecules that are toxic to motor neurons.

Reactive astrocytes may also be stimulated by specific signaling cascades to gain detrimental effects such as the following:

• Exacerbation of inflammation via cytokine production
• Production and release of neurotoxic levels of reactive oxygen species
• Release of potentially excitotoxic glutamate
• The potential contribution to seizure genesis
• Compromise of blood-brain barrier function as a result of vascular endothelial growth factor production
• Cytotoxic edema during trauma and stroke through AQP4 overactivity
• Potential for chronic cytokine activation of astrocytes to contribute to chronic pain

Reactive astrocytes have the potential to promote neural toxicity via the generation cytotoxic molecules such as nitric oxide radicals and other reactive oxygen species, which may damage nearby neurons. Reactive astrocytes may also promote secondary degeneration after CNS injury.