Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Journal of Cerebral Blood Flow and Metabolism |
| Vol/bind | 20 |
| Udgave nummer | 8 |
| Sider (fra-til) | 1174-1189 |
| Antal sider | 15 |
| ISSN | 0271-678X |
| DOI | |
| Status | Udgivet - 2000 |
| Udgivet eksternt | Ja |
Bibliografisk note
Keywords: Animals; Brain; Capillaries; Cerebrovascular Circulation; Cytokines; Encephalitis; Freezing; Growth Substances; Macrophages; Metallothionein; Mice; Mice, Knockout; Microscopy, Electron; Neovascularization, Physiologic; Protein Isoforms; Reference Values; Stem CellsAdgang til dokumentet
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Altered central nervous system cytokine-growth factor expression profiles and angiogenesis in metallothionein-I+II deficient mice. / Penkowa, M; Carrasco, J; Giralt, M; Molinero, A; Hernández, J; Campbell, I L; Hidalgo, J.
I: Journal of Cerebral Blood Flow and Metabolism, Bind 20, Nr. 8, 2000, s. 1174-1189.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - Altered central nervous system cytokine-growth factor expression profiles and angiogenesis in metallothionein-I+II deficient mice
AU - Penkowa, M
AU - Carrasco, J
AU - Giralt, M
AU - Molinero, A
AU - Hernández, J
AU - Campbell, I L
AU - Hidalgo, J
N1 - Keywords: Animals; Brain; Capillaries; Cerebrovascular Circulation; Cytokines; Encephalitis; Freezing; Growth Substances; Macrophages; Metallothionein; Mice; Mice, Knockout; Microscopy, Electron; Neovascularization, Physiologic; Protein Isoforms; Reference Values; Stem Cells
PY - 2000
Y1 - 2000
N2 - To study the importance of metallothionein-I and -II (MT-I+II) for brain inflammation and regeneration, the authors examined normal and MT-I+II knock-out (MT-KO) mice subjected to a cortical freeze injury. Normal mice showed profound neurodegeneration, inflammation, and gliosis around the injury, which was repaired by 20 days postlesion (dpl). However, in MT-KO mice the lesion-associated inflammation was still present as late as 90 dpl. Scanning electron microscopy demonstrated that the number of capillaries was lower, and ultrastructural preservation of the lesioned parenchyma was poorer in MT-KO mice, suggesting an altered angiogenesis. To gain insight into the mechanisms involved, a number of cytokines and growth factors were evaluated. The number of cells expressing the proinflammatory cytokines IL-1beta, IL-6, and TNF-alpha was higher in MT-KO mice than in normal mice, which was confirmed by RNase protection analysis, whereas the number of cells expressing the growth factors bFGF, TGFbeta1, VEGF, and NT-3 was lower. Increased expression of proinflammatory cytokines could be involved in the sustained recruitment of CD-14+ and CD-34+ inflammatory cells and their altered functions observed in MT-KO mice. Decreases in trophic factors bFGF, TGFbeta1, and VEGF could mediate the decreased angiogenesis and regeneration observed in MT-KO mice after the freeze lesion. A role for MT-I+II in angiogenesis was also observed in transgenic mice expressing IL-6 under the control of the promoter of glial fibrillary acidic protein gene (GFAP-IL6 mice) because MT-I+II deficiency dramatically decreased the IL-6-induced angiogenesis of the GFAP-IL6 mice. In situ hybridization analysis indicated that the MT-III expression was not altered by MT-I+II deficiency. These results suggest that the MT-I+II isoforms have major regulatory functions in the brain inflammatory response to injury, especially in the angiogenesis process.
AB - To study the importance of metallothionein-I and -II (MT-I+II) for brain inflammation and regeneration, the authors examined normal and MT-I+II knock-out (MT-KO) mice subjected to a cortical freeze injury. Normal mice showed profound neurodegeneration, inflammation, and gliosis around the injury, which was repaired by 20 days postlesion (dpl). However, in MT-KO mice the lesion-associated inflammation was still present as late as 90 dpl. Scanning electron microscopy demonstrated that the number of capillaries was lower, and ultrastructural preservation of the lesioned parenchyma was poorer in MT-KO mice, suggesting an altered angiogenesis. To gain insight into the mechanisms involved, a number of cytokines and growth factors were evaluated. The number of cells expressing the proinflammatory cytokines IL-1beta, IL-6, and TNF-alpha was higher in MT-KO mice than in normal mice, which was confirmed by RNase protection analysis, whereas the number of cells expressing the growth factors bFGF, TGFbeta1, VEGF, and NT-3 was lower. Increased expression of proinflammatory cytokines could be involved in the sustained recruitment of CD-14+ and CD-34+ inflammatory cells and their altered functions observed in MT-KO mice. Decreases in trophic factors bFGF, TGFbeta1, and VEGF could mediate the decreased angiogenesis and regeneration observed in MT-KO mice after the freeze lesion. A role for MT-I+II in angiogenesis was also observed in transgenic mice expressing IL-6 under the control of the promoter of glial fibrillary acidic protein gene (GFAP-IL6 mice) because MT-I+II deficiency dramatically decreased the IL-6-induced angiogenesis of the GFAP-IL6 mice. In situ hybridization analysis indicated that the MT-III expression was not altered by MT-I+II deficiency. These results suggest that the MT-I+II isoforms have major regulatory functions in the brain inflammatory response to injury, especially in the angiogenesis process.
U2 - 10.1097/00004647-200008000-00003
DO - 10.1097/00004647-200008000-00003
M3 - Journal article
C2 - 10950378
VL - 20
SP - 1174
EP - 1189
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
SN - 0271-678X
IS - 8
ER -