Microglia

In the developing brain, weak synapses are pruned away by microglia involving the neuronal expression of classic complement proteins such as C1q and C3, which tag weak synapses for elimination by complement receptor expressing microglia.

In the hippocampus memory traces are formed and synapse elimination has been linked to diseases of memory in adults.

Microglia mediated synapse elimination underlies the act of forgetting for certain noxious stimuli, at least.

The complement protein C1q colocalizes with synaptic proteins within microglia during normal forgetting.

The act of forgetting is an active process in which weaker synapsis are tagged for removal by microglia, and it occurs throughout life to strengthen networks and retain memories.

Complement and microglia contribute to normal forgetting and indicates that pathological forgetting, as it occurs in dementia is a pathologic remembering as may occur  in post traumatic stress disorder, may be due to the defects in the maintenance of these networks.

Microglia are a type of neuroglia located throughout the brain and spinal cord.

Microglia account for about 10-15% of cells found within the brain.

Microglia are theresident macrophage cells, they act as the first and main form of active immune defense in the central nervous system (CNS).

Microglia and other neuroglia including astrocytes are distributed in large non-overlapping regions throughout the CNS.

Microglia are key cells in overall brain maintenance.

Microglia are constantly scavenging the CNS for plaques, damaged or unnecessary neurons and synapses, and infectious agents.

Microglia are extremely sensitive to even small pathological changes in the CNS, that are achieved in part by the presence of unique potassium channels that respond to even small changes in extracellular potassium.

Microglia are also key players in the sustainment of normal brain functions under healthy conditions, constantly monitor neuronal functions through direct somatic contacts and exert neuroprotective effects when needed, play important roles in maintaining brain function and responding to injury and inflammation. 

They represent the resident immune system of the CNS.

Microglia have many functions, including:

1. Immune response: Like other immune cells, microglia actively participate in the immune response against pathogens, toxins, and other damaging agents in the CNS. 

Microglia can engulf and eliminate foreign molecules, dead cells, and debris in the brain.

2. Inflammation: Microglia release cytokines and other inflammatory molecules that can exacerbate neuroinflammation, which can in turn contribute to the progression of neurodegenerative diseases.

3. Tissue remodeling: Microglia can change shape and position themselves to help shape the brain’s structure and connections.

4. Neuroprotection: Microglia release neurotrophic factors that promote neuron growth and survival.

Microglia may play important roles in brain development and various aspects of brain function from learning to complex behavior. 

Microglial overactivation can contribute to damage and nerve cell death: Alzheimer’s disease, Parkinson’s disease, and stroke.

The brain and spinal cord are not usually accessed directly by pathogenic factors in the body’s circulation due to a series of endothelial cells known as the blood–brain barrier (BBB)>

The BBB prevents most infections from reaching the vulnerable nervous tissue. 

If infectious agents are directly introduced to the brain or cross the blood–brain barrier, microglial cells must react quickly to decrease inflammation and destroy the infectious agents.

Because few antibodies are small enough to cross the blood–brain barrier, 

microglia must be able to recognize foreign bodies, swallow them, and act as antigen-presenting cells activating T-cells.

Microglial cells are extremely plastic, and undergo structural changes based on location and system needs so as to be able to fulfill the vast variety of functions that microglia perform. 

They adopt a specific form, or phenotype, in response to the local conditions and chemical signals they have detected.

The resting form of microglia is composed of long branching processes and a small cellular body. 

The cell body of the ramified form remains in place while its branches are constantly moving and surveying the surrounding area.

Unlike activated or ameboid microglia, ramified microglia do not phagocytose cells and secrete fewer immunomolecules.

Microglia in this state are able to search for and identify immune threats while maintaining homeostasis in the CNS.

In the resting state microglia are active in chemically surveying the environment. 

Ramified microglia can be transformed into the activated form in response to injury or threat.

Microglia can be activated by a variety of factors including: pro-inflammatory cytokines, cell necrosis factors, lipopolysaccharide, and changes in extracellular potassium as indicative of ruptured cells.

Activated microglia cells undergo morphological changes including the thickening and retraction of branches, uptake of MHC proteins, expression of immunomolecules, secretion of cytotoxic factors, secretion of recruitment molecules, and secretion of pro-inflammatory signaling molecules.

Microglia also undergo rapid proliferation in order to increase their numbers.

Activated phagocytic microglia are the immune-responsive form of microglia. 

Activated phagocytic microglia take on a large, ameboid shape.

Activated phagocytic microglia have the antigen presenting, cytotoxic and inflammation-mediating signaling of activated non-phagocytic microglia, they are also able to phagocytize foreign materials and display the resulting immunomolecules for T-cell activation. 

Phagocytic microglia travel to the site of the injury, engulf the offending material, and secrete pro-inflammatory factors to promote more cells to proliferate and do the same. 

Activated phagocytic microglia also interact with astrocytes and neural cells to fight off any infection or inflammation as quickly as possible with minimal damage to healthy brain cells.

Activated phagocytic microglia have free movement throughout the neural tissue, which allows it to fulfill its role as a scavenger cell. 

Amoeboid microglia are able to phagocytose debris, but do not fulfill the same antigen-presenting and inflammatory roles as activated microglia. 

Amoeboid microglia are especially prevalent during the development and rewiring of the brain, when there are large amounts of extracellular debris and apoptotic cells to remove. 

This form of microglial cell is found mainly within the perinatal white matter areas in the corpus callosum.

Gitter cells are the eventual result of microglial cells’ phagocytosis of infectious material or cellular debris. 

After engulfing a certain amount of material, the phagocytic microglial cell becomes unable to phagocytose any further materials, resulting in a cellular mass is known as a granular corpuscle.

By looking at tissue stained to reveal gitter cells, pathologists can visualize healed areas post-infection.

Perivascular microglia are mainly found encased within the walls of the basal lamina. 

Perivascular microglia perform normal microglial functions, but are replaced by bone marrow-derived precursor cells on a regular basis.

They express MHC class II antigens, and react strongly to macrophage differentiation antigens.

Microglia are essential for the repair of vascular walls, as perivascular microglia promote endothelial cell proliferation, allowing new vessels to be formed and damaged vessels to be repaired. 

Juxtavascular microglia have direct contact with the basal lamina wall of blood vessels but are not found within the walls. 

Juxtavascular microglia express MHC class II proteins even at low levels of inflammatory cytokine activity. 

Juxtavascular microglia do not exhibit rapid turnover or replacement with myeloid precursor cells on a regular basis.