The term “necrobiosis” refers to astrocyte death due to acute edema.
When astrocytic processes extending radially break in the process described above, it is called clasmatodendrosis. However, this term is somewhat outdated.
The term “astrocytosis” indicates a state where astrocytes proliferate as a result of some type of tissue damage.
This term refers to a state of astrocyte with a swollen cytoplasm that is induced by increased intermediate filaments of the astrocyte in response to tissue damage. This is a relatively acute reactive change in astrocytes and is also referred to as plump astrocyte. With H&E staining, the cytoplasm is stained eosinophilic and appears evenly swollen, with short thick processes. These astrocytes are stained with GFAP found in glial cell intermediate filaments and vimentin antibodies. The nuclei are generally swollen, and the nucleoli are also clearly visible.
Gemistocytic astrocytes can be observed in various types of tissue damage, particularly Creutzfeldt–Jakob disease and progressive multifocal leukoencephalopathy, which are characterized by very large gemistocytic astrocytes.
Unlike gemistocytic astrocytes, fibrillary astrocytes have abundant fiber components in the processes; however, they have low amount of cytoplasm. The state of fibrillary astrocytes indicates a tissue reaction that leads to gliosis (described below). With H&E staining, eosinophilic (red) fiber components are seen extending from a relatively small amount of cell bodies (soma) in a brush-like fashion. The nuclei are large and clear with distinct nucleoli, and these cells are positively stained with GFAP and vimentin antibodies; the processes can be clearly observed with Holzer staining.
Gliosis refers scarring that occurs when the processes of fibrous astrocytes extend to cover and repair the damaged tissue; it is also called fibrillary gliosis. When the damaged tissue slowly and chronically progresses toward gliosis (as seen in degenerative disease), the astrocytic fiber components imitate the orientation of the original existing fibers and form a scar (gliosis). This is called isomorphic gliosis. In the event of relatively sudden tissue destruction, the astrocytic fibers progress in random directions and do not necessarily imitate the orientation of existing neural fibers. This is referred to as anisomorphic gliosis.
Following cerebral edema, the cytoplasm of astrocytes swells; during this, there is a stage when they appear to have an amoeba-like shape (hence the name amoeboid glia).
The term Alzheimer-type glia refers to astrocytes of the basal ganglia in liver damage due to Wilson’s disease and hepatic encephalopathy that present with large nuclei with a distinct nuclear membrane and nucleoli. Of these, cells with little cytoplasm where only the nucleus is distinct are called type 2 glia or naked glia.
Eosinophilic viral inclusions are sometimes observed in the nuclei of astrocytes infected with cytomegaloviruses. The inclusions appear eosinophilic with H&E staining (red) and are positively immunostained with antibodies against the virus.
Polyglucosan body is a general term, and it accumulates within neurons and glia. Corpora amylacea and amyloid bodies are the typical corptra amylacea, which accumulate in the processes of astrocytes. With H&E staining, they appear as pale dark (gray–blue) eosinophilic bodies, and they are positively stained (red) with PAS staining. CA also accumulates in neuronal processes, which are called intraneuritic corpora amylacea. In general, they occur as age-related changes, are not disease specific, and may be present in any individual if perivascular and pia mater conditions are physically suitable. However, in hippocampal sclerosis, it has recently been reported that corpora amylacea form prior to neuronal loss in the pyramidal cell layer. This suggests that astrocytes play a definite role in neuronal loss, and further examination is required.
Rosenthal fibers are clubbed vitreous structures that are stained eosinophilic with H&E staining and are formed in astrocytic processes. They present as bundles consisting of astrocytic fibers and are therefore stained blue with PTAH. They are positively stained with anti-GFAP and antivimentin antibodies and are generally found in old areas of gliosis and in gliomas. On the other hand, Rosenthal fibers are clinically significant in Alexander’s disease because many appear in astrocytic end-feet, which extend to blood vessels, pia mater, and throughout the brain.
Glial bundles are positively immunostained with anti-GFAP antibodies and are formed in the ventral spinal nerve root and occasionally in the dorsal root in Werdnig–Hoffmann disease. Thus, they are diagnostically significant.
Astrocytes located in the Purkinje cell layer of the cerebellum are specifically called Bergmann’s glia. Gliosis at sites of Purkinje cell degeneration is referred to as Bergmann’s glial proliferation. Bergmann’s glia have a small cell body; therefore, prominent large proliferating nuclei that appear in a row with Purkinje cell loss in the cerebellar cortex are Bergmann’s glial nuclei.
Neurodegenerative diseases caused by abnormal accumulation of phosphorylated tau proteins (i.e., tauopathy) have recently drawn much attention. However, in some of these diseases, the abnormal deposition of phosphorylated tau has been found in neurons and glial cells. Of these, astrocytes with abnormal tau deposits present several different morphologies depending on the staining method, including GB and immunostaining with antitau antibodies. These morphologies include thorn-shaped astrocytes, tuft-shaped astrocytes, and astrocytic plaques, which cannot be visualized with H&E and Bodian silver staining and have therefore not been noticed until recently. Various patterns are detected in tauopathies, such as PSP and CBD. Moreover, similar accumulation is found in extra-astrocytic glial cells (i.e., oligodendroglia), as described in a separate section.
Thorn-shaped astrocytes contain aggregates of tau proteins in processes extending from the cell body and appear short and thick when stained using the GB method and immunostained with antiphospho-tau antibodies. They do not specifically appear in tauopathy and do not have any significance for differential diagnoses.
Tuft-shaped astrocytes contain abnormal phosphorylated tau aggregates in portions of astrocytic processes near the cell body and appear like a tuft. They cannot be observed with routine H&E and Bodian staining but were observed for the first time with GB and antiphospho-tau immunostaining. Identification of tuft-shaped astrocytes underlies the pathological diagnosis of PSP.
Astrocytic plaques contain abnormal aggregates of phosphorylated tau in the distal portion of astrocytic processes and appear patchy or wreath-like as a whole. Like tuft-shaped astrocytes, astrocytic plaques cannot be visualized with routine H&E and Bodian stains and were first observed with GB and antiphospho-tau immunostaining. These structures are used as a pathological diagnostic marker for CBD.
Dysplastic disorders of the brain include diseases with neural and glial cell atypia. Very large odd-shaped glial cells that may to be derived from astrocytes are called grotesque cells or bizarre glial cells. They appear similar to gemistocytic astrocytes with H&E staining, with abundant eosinophilic (red) cell bodies, and they are positively stained with anti-GFAP and antivimentin antibodies. They are found in lesion sites in focal cortical dysplasia and tuberous sclerosis.
While rarely reported, polymicrogyria aggregates of eosinophilic inclusions have been found in astrocytes in some diseases. They have also been reported in Aicardi syndrome. Further reports describing such inclusions have also been found in normal healthy individuals without polymicrogyria.
In 1987, Arai et al. first described countless foamy spheroid bodies in the degenerate substantia nigra zona reticularis in an autopsy case with narcolepsy. As the name suggests, foamy spheroid bodies are foamy spheroid structures approximately 10–50 μm in diameter that have an indistinct border and almost no affinity for H&E. Some contain relatively coarse eosinophilic granular structures. Subsequent studies have revealed that foamy spheroid bodies commonly appear in the substantia nigra zona reticularis as well as the inner segment and most ventral portion of the pallidum below the anterior commissure and develop in degenerative disease and with normal aging.
Electron microscopic tests and immunostaining have shown that foamy spheroid bodies are surrounded by astrocyte intermediate filament bundles and punctate adhesions between astrocytic processes. In addition, they contain neurofilaments; therefore, products derived from destroyed neurons are thought to be surrounded by astrocytic processes. The inner portion of these bodies is clearly stained with antiubiquitin antibodies; therefore, it is thought to contain degenerated ubiquitinated proteins. Foamy spheroid bodies can be easily missed at the first glance. However, in bodies that contain rather large, coarse, granular structures, the inner tissue appears coarse and spheroid. Consequently, they have long been mistaken for axonal swelling and dystrophic axons, in particular.
