Expression of TGF- isoforms, their receptors and related SMAD proteins in brain pathology : Immunohistochemical studies focusing on infarcts, abscesses and malignant gliomas

Sammanfattning: This thesis focuses on the immunohistochemical expression of transforming growth factor beta(TGFβ) isoforms, their receptors and TGF-β-related SMAD proteins in brain pathology, chiefly in-farcts. One key question was whether the expressions of these compounds are altered within glial cells, endothelial cells of microvessels and other cell types in the vicinity of infarcts. Studies on human and animal brain infarcts were made. Immunoreactivities to TGF-β isoforms -β1, -β2 and -β3, and TGF-βreceptor (TβR) type I were seen in astrocytes, macrophages, neurons, endothelial and vascular smooth muscle cells of human brain infarcts. Similar observations were made in an experimental model of rat brain infarct at day 1 and 3 following occlusion of the middle cerebral artery (MCA). Increased expression of Smad2, -3, -4, -6 and -7 was seen already at 6 h after MCA occlusion in neurons, microvascular endothelial cells, astroglial cells and inflammatory cells. Later on, immunopositive macrophages were present in the infarcts. The changes persisted even at day 7 after MCA occlusion.Several alterations thus occur during the evolution of brain infarcts with regard to the immuno­histochemical expression of TGF-β, its receptors and related SMAD proteins. Such changes are, however, not unique to brain infarcts. Thus, patterns of high expression for TGF-β- isoforms -β1, -β2 -β3, and TβR-I in cases of brain abscess (human), and of Smad2, -3, -4, -6 and -7 in tumor cells and neoplastic blood vessels of malignant gliomas (human) were also observed.In addition, immunohistochemical expression of vascular endothelial growth factor (VEGF) andits receptors was investigated since this growth factor is involved in angiogenesis and edemaformation, two cardinal features of brain infarcts. Increased immunoreactivities, seen particularly in the edges of infarcts, were observed already at day 1 after MCA occlusion.In conclusion, the various TGF-β isoforms, receptors and related SMAD proteins, together with other factors, seem to be involved in the very complicated and important changes taking place in the vicinity of brain infarcts.