Unusual topographical pattern of proximal astrogliosis around a cortical devascularizing lesion.
Class II vessels were disrupted on the cortical surface of adult rats within a circular 5-mm-diameter area. This consistently resulted in the formation of a conical lesion by day 1, with a cystic cavity forming by day 21. Four markers were used to identify the glial response surrounding the lesion. The antibody used against S100beta marked the largest astrocytic pool in the gray matter of the cerebral cortex; only approximately 5% of astrocytes were glial fibrillary acidic protein (GFAP)(+) in control animals. GFAP served as a marker for distal reactive gliosis and vimentin (VIM) for proximal gliosis. Isolectin B4 was used as an additional marker to distinguish VIM(+) microglia from astrocytes inside the lesion area. Three immunohistochemically distinct areas of reactive astrocytes surrounding the lesion were found within 24 hr of injury and lasted through day 6. The first area, in contrast to focal traumatic injuries, consisted of a 196-microm-thick boundary layer of S100beta(+) cells immediately surrounding the lesion that never expressed GFAP or VIM by day 6. This boundary layer turns into a GFAP(+) glial limitans encasing the cystic cavity by day 21. A second unusual extended area around the base of the lesion reaching partly into the corpus callosum consisted of S100beta(+)/GFAP(+)/VIM(+) cells. This region appears to be compatible with the local or proximal gliotic response usually found completely surrounding other focal-type injuries. The proximal response at the base of the lesion developed over the first 3 days in the following sequence: S100beta(+)/GFAP(-)/VIM(-) to S100beta(+)/GFAP(+)/VIM(-) to S100beta(+)/GFAP(+)/VIM(+). Ninety percent of the astrocytes in this area express VIM. This is very high compared with findings in stab-wound preparations, where only 10% of astrocytes (surrounding entire lesion) are found to be VIM(+). A third region, consistent with a remote or distal reactive gliotic response, demonstrated staining for S100beta and had increased GFAP contents throughout the neocortical hemisphere. Cells in this region were never found to be VIM(+). Among S100beta(+) cells close to the boundary region, more than 80% expressed detectable GFAP by 2 days after lesioning. S100beta(+) cells 1 mm more laterally (distal to lesion) did not express GFAP to the same level until day 6. Thus, we find three immunohistochemically distinct populations of reactive astrocytes surrounding the focal ischemic lesion. In contrast to the case for stab-wound traumatic injury, the response closest to and surrounding the lesion did not up-regulate GFAP or VIM by day 6. The proximal response was, instead, more remote and only at the base of the lesion, extending partly into the corpus callosum.
Wang
Kai
K
Department of Physiology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Walz
Wolfgang
W
D000818:Animals; D002452:Cell Count; D002540:Cerebral Cortex / Q000098:blood supply / Q000293:injuries / Q000378:metabolism / Q000473:pathology*; D020214:Cerebrovascular Trauma / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique / Q000379:methods; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000378:metabolism* / Q000473:pathology; D037102:Lectins / Q000378:metabolism; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism; D013194:Staining and Labeling / Q000379:methods; D013997:Time Factors; D014659:Vasectomy / Q000379:methods; D014746:Vimentin / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; D037102:Lectins; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D014746:Vimentin