REACTIONS OF ASTROCYTES TO INJURY

The cellular pathology of astrocytes may be subdivided into reactive responses that accompany the cells' proliferation (gliosis) and the sets of reactions to injury that lead to their death.

In addition, morphologically diverse intracellular inclusions and deposits are seen in injured astrocytes.

• Gliosis is the most important histopathologic indicator of CNS injury, regardless of etiology. Astrocytes participate in this process by undergoing both hypertrophy and

hyperplasia. The nucleus enlarges and becomes vesicular, and the nucleolus is prominent. The previously scant cytoplasm expands to a bright pink, somewhat irregular swath

around an eccentric nucleus, from which emerge numerous stout, ramifying processes (gemistocytic astrocyte). Immunohistochemistry for glial fibrillary acidic protein (GFAP)

splendidly demonstrates the extraordinary metamorphosis. In long-standing lesions, the nuclei become small and dark and lie in a dense net of processes. These cell processes,

glial "fibrils," are not true extracellular fibers. Proliferation of astrocytes residing between the molecular and granule cell layers of the cerebellum is a regular accompaniment of

anoxic injury and other conditions associated with death of Purkinje cells, termed Bergmann gliosis.

• Cellular swelling, or swelling of the astrocyte cytoplasm, occurs regularly in acute insults when there is a failure of the cell's pump systems, as occurs in hypoxia,

hypoglycemia, and toxic injuries.[13]

• Rosenthal fibers are thick, elongated, brightly eosinophilic structures that are somewhat irregular in contour and occur within astrocytic processes. Ultrastructurally, they

exhibit dense osmiophilic deposits that contain two heat-shock proteins (aB-crystallin and hsp27) and ubiquitin. Rosenthal fibers are typically found in regions of long-standing

gliosis; they are also characteristic of cerebellar pilocytic astrocytoma (see later), as well as the reactive brain adjacent to craniopharyngioma or syrinx cavities. In Alexander

disease, a leukodystrophy due to a mutation in the gene for GFAP,[14]abundant Rosenthal fibers are found in periventricular, perivascular, and subpial locations.

• Corpora amylacea, or polyglucosan bodies, are round, faintly basophilic, periodic acid-Schiff (PAS)-positive, concentrically lamellated structures ranging between 5 and 50

μm in diameter and located wherever there are astrocytic end processes, especially in the subpial and perivascular zones. Although consisting primarily of glycosaminoglycan

polymers, they also contain heat-shock proteins and ubiquitin. They represent a degenerative change in the astrocyte, and they occur in increasing numbers with advancing age

and in a rare condition called adult polyglucosan body disease. The Lafora bodies that are seen in the cytoplasm of neurons (as well as hepatocytes, myocytes, and other cells) in

myoclonic epilepsy (Lafora body myoclonus with epilepsy) are of similar structure and biochemical composition.

• Glial cytoplasmic inclusions consisting of silver-positive meshes of 20- to 40-nm intermediate filaments that contain the protein a-synuclein[15] are characteristic of a number

of CNS degenerative diseases, collectively known as multiple system atrophy. [16]

• The Alzheimer type II astrocyte is a gray matter astrocyte with a large (two to three times normal) nucleus, pale-staining central chromatin, an intranuclear glycogen droplet,

and a prominent nuclear membrane and nucleolus. Despite its name, it is unrelated to Alzheimer disease; rather, it occurs especially in patients with long-standing

hyperammonemia due to chronic liver disease, Wilson disease, or hereditary metabolic disorders of the urea cycle.

Date: 2016-04-22; view: 800