Glial function (and dysfunction) in the normal & ischemic brain

Abstract

Astrocytes are the most abundant cell type in the central nervous system (CNS). Once considered to be of fairly homogeneous phenotype throughout the brain and spinal cord, they are now understood to be heterogeneous in both structure and function. They are important in brain functions as diverse as ion and fluid balance in the interstitial space, contributing to integrity of the neurovascular unit (blood-brain barrier), neurotransmitter regulation, metabolism of energy substrates and possibly even axonal regeneration. After ischemic or hemorrhagic brain/spinal cord injury, formation of an astrocytic scar adjacent to the 'lesion' is a characteristic histopathologic feature, and this astrogliosis can be demonstrated by immunohistochemistry, usually using primary antibodies to glial fibrillary acidic protein (GFAP). Astrocytes interact with microglia and oligodendroglia in novel ways that will be discussed in this review. This article is part of the Special Issue entitled 'Cerebral Ischemia'.

Keywords: Astrocytes; Brain injury - responses; Intracerebral hemorrhage; Ischemia; Microglia; Oligodendroglia.

Fig. 1.

A. Activated microglia adjacent to a region of ischemia (surgical specimen), highlighted by immunohistochemistry using anti-CD68. Note variable morphologies, including rounded, triangular and ‘spindled’ cells. B. Astrocytes prominently labelled with anti-GFAP. Cells have variable amounts of cytoplasm and prominent processes. Arrows indicate a blood vessel (which itself is GFAP negative) surrounded by GFAP-immunoreactive astrocytic processes. (Panels A and B are micrographs from the same surgical specimen, photographed at identical magnifications) C. Prominently GFAP-immunoreactive cells with abundant cytoplasm (gemistocytes). D. More star-shaped astrocytes (GFAP immunostain) with relatively little cytoplasm. Arrow indicates a small vessel encircled by astrocytic processes.

Fig. 2.

A. Remote or ‘old’ cystic infarct in cortex lateral to the basal ganglia (visible at right of the micrograph; all images are different views and magnifications of the same infarct). Arrows indicate a cystic cavity representing the infarct. Arrowheads indicate preserved layer I of the cortex, a characteristic finding in old ‘strokes’. B. Magnified view of the infarct shows the cystic cavity replete with lipid-laden macrophages; arrows indicate the preserved and clearly outlined layer I of the cortex, immediately underlying leptomeninges. C. Deep ‘margin’ of the cystic infarct shows abundant astrocytes, including gemistocytes, with prominent eosinophilic cytoplasm. D. Magnified view of the interface between preserved cortical layer I (bottom of the image) and lipid laden macrophages (at top of the image). Subarachnoid space is at the bottom edge of the micrograph. Arrows indicate two gemistocytes with prominent cell processes. [All images are from sections stained with hematoxylin and eosin/H&E].

Fig. 3.

A. Old cortical microhemorrhage, probably related to amyloid angiopathy, in an elderly patient. The neuropil appears cystic, there is slight indentation of the pial surface (secondary to underlying tissue loss) and hemosiderin-laden macrophages are seen in abundance. Arrows indicate extension of the microhemorrhage into the subarachnoid space. B. Magnified view from edge of the brain microbleed (BMB). Arrow indicates a gemistocyte that has either phagocytosed altered blood pigment, or shows it encrusted on the cell membrane. (Images are from H&E-stained sections).

Fig. 4.

A. Linear thalamic hemorrhage, probably of hypertensive origin (indicated by arrows), in an elderly female subject. By history, the ‘stroke’ had occurred several weeks/months prior to autopsy. Large vessel at the center of the hematoma shows significant arteriosclerotic change and may have been the ‘vessel of origin’ of the bleed. Hematoma itself shows preserved erythrocytes at center of the hematoma, but significant hemosiderin-laden macrophages at its margins. B. Magnified view of edge of the hematoma highlighting hemosiderin-laden macrophages and numerous astrocytes. The ‘vacuolated’ cells indicated by arrows probably represent Wallerian degeneration in fiber tracts injured by the hematoma. C. Arrow indicates an arteriosclerotic vessel in close proximity to the hematoma. Note numerous reactive astrocytes; upper right of the micrograph shows macrophages containing altered blood pigment. (Images are from H&E-stained sections).