Microglia and macrophages are major sources of locally produced transforming growth factor-beta1 after transient middle cerebral artery occlusion in rats
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Microglia and macrophages are major sources of locally produced transforming growth factor-beta1 after transient middle cerebral artery occlusion in rats. / Lehrmann, E; Kiefer, R; Christensen, Thomas; Toyka, K V; Zimmer, J; Diemer, Nils Henrik; Hartung, H P; Finsen, B.
In: Glia, Vol. 24, No. 4, 12.1998, p. 437-48.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Microglia and macrophages are major sources of locally produced transforming growth factor-beta1 after transient middle cerebral artery occlusion in rats
AU - Lehrmann, E
AU - Kiefer, R
AU - Christensen, Thomas
AU - Toyka, K V
AU - Zimmer, J
AU - Diemer, Nils Henrik
AU - Hartung, H P
AU - Finsen, B
PY - 1998/12
Y1 - 1998/12
N2 - The potentially neurotrophic cytokine transforming growth factor-beta1 (TGF-beta1) is locally expressed following human stroke and experimental ischemic lesions, but the cellular source(s) and profile of induction have so far not been established in experimental focal cerebral ischemia. This study presents the time course and a cellular localization of TGF-beta1 mRNA, visualized by in situ hybridization combined with immunohistochemical staining for microglia, macrophages, or astrocytes, on brain sections from adult spontaneously hypertensive rats subjected to transient proximal occlusion of their middle cerebral artery. Six hours after ischemia, an early and transient neuronal and microglial expression of TGF-beta1 mRNA was observed in the extraischemic cingulate and frontal cortices. Both early and protracted expression of TGF-beta1 mRNA in the caudate-putamen and neocortical infarcts and in the caudate-putamen penumbra colocalized with OX42/ED1-immunoreactive microglia and macrophages, whereas TGF-beta1 mRNA in the neocortical penumbra colocalized with OX42/ED1-immunoreactive cells of a microglial morphology. No astrocytes were double-labeled. The number of TGF-beta1 mRNA-expressing microglia and macrophages increased strongly during the first week. Thereafter, TGF-beta1 mRNA became increasingly restricted to the neocortical penumbra (3 weeks), and after 3 months it was confined to activated microglia in the anterior commissure. Our data establish activated microglia and macrophages as the major source of TGF-beta1 mRNA following experimental focal cerebral ischemia. Consequently, TGF-beta1-mediated functions may be exerted by microglia both in the early degenerative phase, and later in combination with blood-borne macrophages, in the remodeling and healing phase after focal cerebral ischemia.
AB - The potentially neurotrophic cytokine transforming growth factor-beta1 (TGF-beta1) is locally expressed following human stroke and experimental ischemic lesions, but the cellular source(s) and profile of induction have so far not been established in experimental focal cerebral ischemia. This study presents the time course and a cellular localization of TGF-beta1 mRNA, visualized by in situ hybridization combined with immunohistochemical staining for microglia, macrophages, or astrocytes, on brain sections from adult spontaneously hypertensive rats subjected to transient proximal occlusion of their middle cerebral artery. Six hours after ischemia, an early and transient neuronal and microglial expression of TGF-beta1 mRNA was observed in the extraischemic cingulate and frontal cortices. Both early and protracted expression of TGF-beta1 mRNA in the caudate-putamen and neocortical infarcts and in the caudate-putamen penumbra colocalized with OX42/ED1-immunoreactive microglia and macrophages, whereas TGF-beta1 mRNA in the neocortical penumbra colocalized with OX42/ED1-immunoreactive cells of a microglial morphology. No astrocytes were double-labeled. The number of TGF-beta1 mRNA-expressing microglia and macrophages increased strongly during the first week. Thereafter, TGF-beta1 mRNA became increasingly restricted to the neocortical penumbra (3 weeks), and after 3 months it was confined to activated microglia in the anterior commissure. Our data establish activated microglia and macrophages as the major source of TGF-beta1 mRNA following experimental focal cerebral ischemia. Consequently, TGF-beta1-mediated functions may be exerted by microglia both in the early degenerative phase, and later in combination with blood-borne macrophages, in the remodeling and healing phase after focal cerebral ischemia.
KW - Animals
KW - Arterial Occlusive Diseases
KW - Cerebral Arteries
KW - Gene Expression
KW - Ischemic Attack, Transient
KW - Macrophages
KW - Male
KW - Microglia
KW - RNA, Messenger
KW - Rats
KW - Rats, Inbred SHR
KW - Transforming Growth Factor beta
M3 - Journal article
C2 - 9814824
VL - 24
SP - 437
EP - 448
JO - GLIA
JF - GLIA
SN - 0894-1491
IS - 4
ER -
ID: 45392436