STRUCTURAL ALTERATIONS AND CHANGES IN CYTOSKELETAL PROTEINS AND PROTEOGLYCANS AFTER FOCAL CORTICAL ISCHEMIA

In order to study structural alterations which occur after a defined u nilateral cortical infarct, the hindlimb region of the rat cortex was photochemically lesioned. The infarcts caused edema restricted to the perilesional cortex which affected allocortical and isocortical areas differently. Postlesional changes in cytoskeletal marker proteins such as microtubule-associated protein 2, non-phosphorylated (SMI32) and p hosphorylated (SMI35, SMI31 and 200,000 mol. wt) neurofilaments and 14 6,000 mel. art glycoprotein Py as well as changes in proteoglycans vis ualized with Wisteria floribunda lectin binding (WFA) were studied at various time points and related to glial scar formation. The results o btained by the combination of these markers revealed six distinct regi ons in which transient, epitope-specific changes occurred: the core, d emarcation zone, rim, perilesional cortex, ipsilateral thalamus and co ntralateral homotopic cortical area. Within the core immunoreactivity for microtubule-associated protein 2 and SMI32 decreased and the cellu lar components showed structural disintegration 4 h post lesion, but p artial recovery of somatodendritic staining was seen after 24 h. Micro tubule-associated protein 2 and SMI32 persisted up to days 7 and 5 res pectively in the core, whereas the number of glial fibrillary acidic p rotein-and WFA-positive cells decreased between days 7 and 14. The dem arcation zone showed a dramatic loss of immunoreactivity for all epito pes 4 h post lesion which was not followed by a phase of recovery. In the inner region of the demarcation zone there was an invasion and acc umulation of non-neuronal WFA-positive cells which formed a tight caps ule around the core. Neuronal immunoreactivities for microtubule-assoc iated protein 2, SMI31 and Py as well as astrocytic glial fibrillary a cidic protein increased strongly within an approximately 0.4-1.0 mm-wi de rim region directly bordering the demarcation zone. Py immunoreacti vity increased significantly in the perilesional cortex, whereas glial fibrillary acidic protein-positive astrocytes became transiently more numerous in the entire lesioned hemisphere including strongly enhance d immunoreactivity in the thalamus by days 5-7 post lesion. Glial fibr illary acidic protein immunoreactivity increased in the corpus callosu m and the homotopic cortical area of the unlesioned hemisphere by days 5-7. In this homotopic area additional changes in SMI31 immunoreactiv ity occurred. Our results showed that a cortical infarct is not only a locally restricted lesion, but leads to a variety of cytoskeletal and other structural changes in widely-distributed functionally-related a reas of the brain. (C) 1997 IBRO. Published by Elsevier Science Ltd.