Immunohistochemical study of glial reaction and serum-protein extravasation in relation to neuronal damage in rat hippocampus after ischemia.
Transient forebrain ischemia of 30 min duration was produced in anaesthetized rats by four-vessel occlusion. After survival periods of 3 h to three days brains were perfusion-fixed and sections through the mid-dorsal hippocampus were processed for conventional staining and immunohistochemical analysis. Neuronal damage in the hilus was manifested 3-8 h after ischemia; neurons in the CA1 and CA2 sector suffered delayed neuronal death after 48-72 h whereas the dentate gyrus and the CA3 sector were normal. Vasogenic edema formation was visualized using antibodies against rat serum-proteins, serum albumin and immunoglobulins. By 3 h after ischemia, only faint and diffuse serum-staining was detected. At 8 h survival, weak astrocytic-staining was present. After 24-72 h CA1-CA2 exhibited massive serum extravasation. The molecular layer of the dentate gyrus showed edema formation in the absence of granule cell damage. The glial reaction was studied using antibodies against glial fibrillary acidic protein, vimentin and S-100 protein. Glial fibrillary acidic protein and S-100 protein-staining increased in areas with either edema or neuronal damage. In contrast, changes in vimentin were only detected in areas with neuronal necrosis. The observations demonstrate that following 30 min of ischemia neuronal damage is accompanied by changes in blood-brain barrier function and reactive glial alterations. The dissociation between neuronal necrosis and astroglial hypertrophy and hyperplasia reflects differences in cellular responsiveness which constitute inherent features of postischemic hippocampal injury.
Max-Planck-Institute for Neurological Research, Department for Experimental Neurology, Köln, F.R.G.
R
R
Schmidt-Kastner
J
J
Szymas
K A
KA
Hossmann
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology*; D002199:Capillary Permeability; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D009457:Neuroglia / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains; D009418:S100 Proteins / Q000378:metabolism; D013194:Staining and Labeling; D014746:Vimentin / Q000378:metabolism
D001798:Blood Proteins; D005904:Glial Fibrillary Acidic Protein; D009418:S100 Proteins; D014746:Vimentin