Microglia are a type of glial cell that are the resident macrophages of the brain and spinal cord, and thus act as the first and main form of active immune defense in the central nervous system (CNS). Under normal conditions, microglia remain in a quiescent state, and become metabolically active and mobile under stimulation. Artificial and natural activation includes a wide number of conditions, including microbial invasion, heavy metal toxicity, immune activation, trauma, and a wide number of pharmacologic agents. The activation is short lived, and the microglia behave like immune cells, releasing cytokines and other factors as an immune response. Microglia can also undertake phagocytic activity, removing cellular debris or microorganism remains, as well as soluble beta-amyloid. Their motility allows them to target the synaptic interface between neurons.
Static activation, where microglia do not return to their normal state, can cause substantial damage, including to dendrites and synaptic connections. This chronic microglial activation has been associated with numerous pathological conditions, including Down’s syndrome, autism, neurodegenerative diseases, CNS trauma and infections, over-vaccination, and neurotoxcity including heavy metal and pesticide exposure.
A large number of growth factors and cytokines can enhance exitotoxicity, including TNF-alpha, IL-1ß, IL-2, IL-4, IL-6 and IL-18, interferons and other immune molecules, with TNF-alpha and IL-1ß increased in autism and nearly all of the neurodegenerative diseases. When microglia are activated, they also secrete two known excitotoxins-glutamate and quinolinic acid.
Pharmacologic agents like NSAIDS are known to be potent inhibitors of microglial activation, particularly chronic microglial activation.
Histology approaches in microglial research
The first ability to view and characterize different neural cells including microglia began in 1880 when Nissl staining was developed by Franz Nissl, and showed that microglia are related to macrophages. There are a wide number of IHC and histology staining approaches that can be applied. Some of these neurological IHC antibodies have been worked up previously, others can be developed upon request.
Quantitation approaches in microglial research
Given Flagship’s ability in histology neuronal sectioning combined with Feature Analysis in Consecutive Sections or multiplexed staining in brightfield or fluorescence, many multiplexed evaluations are possible.
Image analysis microglial endpoints using Flagship’s sophisticated algorithms can include detection of microglial soma, the number of activated, inactivated and negative cells, average process area, length, number of branch points, or thickness on a per cell basis.