Neuroinflammation is characterized by extensive astrogliosis, microglial activation, infiltration of peripheral immune cells at sites of neurodegeneration, and increased expression of many immune-related genes. Evidence suggests that neuroinflammation is not a secondary consequence to motor neuron injury, but that it is directly involved in motor neuron death.
Astrogliosis is a somewhat enigmatic event that occurs upon insult such as neurodegeneration, injury, or stroke. It is characterized by astrocyte proliferation and specific structural and functional changes in astrocytes. The best-known hallmark of astrocyte activation is upregulation of the intermediate filament protein, glial fibrillary acidic protein (GFAP). Upregulation of GFAP and other intermediate filament proteins is accompanied by changes in gene expression that varies from neuroprotective to neurotoxic depending on the type of insult (such as neuroinflammation or ischemic injury). In ALS astrogliosis is not restricted to areas of motor neuron death such as the ventral horn of the spinal cord and the cortical motor cortex. In fact, it also occurs in the dorsal horn and cortical white mater.
Microglia, the myeloid cells of the CNS, normally exist in a surveying state, actively monitoring the CNS. After sensing activating stimuli such as injury, infection, or neurodegeneration, microglia rapidly change their morphology from highly ramified cells to more amoeboid-like cells with bigger somas and shorter, thickened processes.