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 t he right internal carotid artery, and structural changes in the astrocytes were observed during the early period following the infarction. Necrotic fo ci, varying in size and shape, were found in the right hemisphere. After im munohistochemical staining for GFAP GFAP-positive astrocytes in the perinec rotic area known as the ischemic penumbra had distinctly increased in numbe r and size with elongation of cytoplasmic processes 3 days after infarction . Electron microscopic observation revealed that glycogen granules had mark edly accumulated in the cytoplasm of astrocytes located in the ischemic pen umbra 3 and 5 days after infarction. Seven days after infarction, however, the glycogen granules disappeared from the astrocytes. Intermediate filamen ts increasingly appeared in the protoplasmic astrocytes after 3 days and we re abundant in the activated and hypertrophied astrocytes after 7 days. As a result of our present study, we conclude that: (1) the function of glucos e uptake from blood the vessels was not impaired in the astrocytes under hy poxic conditions; (2) the astrocytes actively ingested blood glucose throug h 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 so urces in the nerve cells promoted glycogen accumulation in the astrocytes u nder hypoxic conditions; (4) intermediate filaments (GFAP filaments) increa sed in number, coincident with the activation and enlargement of the astroc ytes; and (5) protoplasmic astrocytes were transformed into fibrous astrocy tes in the ischemic penumbra of the brain infarction. (C) 2001 Elsevier Sci ence B.V. All rights reserved.