Reactive astrocytes involved in the formation of lesional scars differ in the mediobasal hypothalamus and in other forebrain regions

Abstract

The fine organization of lesional scars was studied in adult rats at the level of 2 types of surgical cuts aimed at deafferentating the dorsal hypothalamus from its neuropeptide-Y innervation. These included: (i) lesions located dorsolateral to the dorsal hypothalamus, which were shown to form a permanent obstacle to the regeneration of transected neuropeptide-Y-fibers, and (ii) lesions located in the ventromedial hypothalamus, where transected neuropeptide-Y-fibers were shown to penetrate and eventually cross the lesional area. Double labeling immunocytochemistry and conventional electron microscopy were used to identify various molecules produced by reactive astrocytes and to visualize their ultrastructural organization within the scars, respectively. In the different portions of the dorsolateral scars, the large majority of reactive astrocytes was characterized by a strong immunoreactivity to glial fibrillary acidic protein, vimentin, and embryonic (polysialylated) NCAM. Intense laminin-immunoreactivity was also observed over large patches included in the scar. Electron microscope observations further indicated that the matrix of the scar was mainly composed of tightly packed astrocytic perikarya and processes connected by extended gap junctions. All around the extracellular and perivascular spaces, these astrocyte profiles were bordered by a thick basal lamina. Only scarce axonal profiles were detected in the core of the scar, most of which exhibited degenerative features. In the ventromedial hypothalamic scars, reactive astrocytes were found to exhibit intense immunoreactivity to both glial fibrillary acidic protein and vimentin. On the other hand, only slight immunostaining to embryonic NCAM and laminin were associated with this type of lesional scar. At the ultrastructural level, the main differences with the dorsolateral scars concerned (i) the gap junctions, which were less frequent and involved shorter portions of adjacent membranes; (ii) the basal lamina, which was essentially localized to the perivascular spaces; and (iii) the axonal profiles, which were frequently observed throughout the scar matrix. These data indicate that reactive astrocytes that formed the glial scar differ in the mediobasal hypothalamus and in other forebrain regions. This provides strong support for the hypothesis that the regeneration of neuropeptide-Y axons through a mediobasal hypothalamic surgical cut depends mainly on the particular organization of the astroglial scar.