Activated astrocytes with glycogen accumulation in ischemic penumbra during the early stage of brain infarction: immunohistochemical and electron microscopic studies.

Brain infarction was induced in rats by injection of microspheres through the right internal carotid artery, and structural changes in the astrocytes were observed during the early period following the infarction. Necrotic foci, varying in size and shape, were found in the right hemisphere. After immunohistochemical staining for GFAP, GFAP-positive astrocytes in the perinecrotic area known as the ischemic penumbra had distinctly increased in number and size with elongation of cytoplasmic processes 3 days after infarction. Electron microscopic observation revealed that glycogen granules had markedly accumulated in the cytoplasm of astrocytes located in the ischemic penumbra 3 and 5 days after infarction. Seven days after infarction, however, the glycogen granules disappeared from the astrocytes. Intermediate filaments increasingly appeared in the protoplasmic astrocytes after 3 days and were abundant in the activated and hypertrophied astrocytes after 7 days. As a result of our present study, we conclude that: (1) the function of glucose uptake from blood vessels was not impaired in the astrocytes under hypoxic conditions; (2) the astrocytes actively ingested blood glucose through the endothelial cells and accumulated it as glycogen for activation of their functions, and the cell volume increased under hypoxic conditions; (3) the depression of energy metabolism and the decrease in the uptake of energy sources in the nerve cells promoted glycogen accumulation in the astrocytes under hypoxic conditions; (4) intermediate filaments (GFAP filaments) increased in number, coincident with the activation and enlargement of the astrocytes; and (5) protoplasmic astrocytes were transformed into fibrous astrocytes in the ischemic penumbra of the brain infarction.