Differential neuronal and astrocytic expression of transforming growth factor beta isoforms in rat hippocampus following transient forebrain ischemia

Knuckey, Neville W.; Finch, Paul W.; Palm, Donald E.; Primiano, Michael J.; Johanson, Conrad E.; Flanders, K. C.; Thompson, Nancy L.

doi:10.1016/0169-328x(96)00016-2

Cited by 76 publications

(79 citation statements)

References 60 publications

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“…TGF-β1 immunoreactivity was present at 7 and 14 dpi in cerebellum (Figure 2), cortex, brain stem, and spinal cord (data not shown), which are brain regions highly susceptible to T cell infiltration and demyelination. Double immunolabeling and confocal microscopy identified microglia ( Figure 2D) and astrocytes ( Figure 2E) as the main TGF-β1-producing cells, consistent with previous reports in acute brain injury (29,30). CD4 + T cells showed no significant TGF-β1 immunoreactivity at 7 ( Figure 2F) or 14 dpi (not shown).…”

Section: Figuresupporting

confidence: 77%

Glia-dependent TGF-β signaling, acting independently of the TH17 pathway, is critical for initiation of murine autoimmune encephalomyelitis

Luo¹,

Ho²,

Buckwalter³

et al. 2007

J. Clin. Invest.

109

111

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Autoimmune encephalomyelitis, a mouse model for multiple sclerosis, is characterized by the activation of immune cells, demyelination of axons in the CNS, and paralysis. We found that TGF-β1 synthesis in glial cells and TGF-β-induced signaling in the CNS were activated several days before the onset of paralysis in mice with autoimmune encephalomyelitis. While early production of TGF-β1 was observed in glial cells TGF-β signaling was activated in neurons and later in infiltrating T cells in inflammatory lesions. Systemic treatment with a pharmacological inhibitor of TGF-β signaling ameliorated the paralytic disease and reduced the accumulation of pathogenic T cells and expression of IL-6 in the CNS. Priming of peripheral T cells was not altered, nor was the generation of TH17 cells, indicating that this effect was directed within the brain, yet affected the immune system. These results suggest that early production of TGF-β1 in the CNS creates a permissive and dangerous environment for the initiation of autoimmune inflammation, providing a rare example of the brain modulating the immune system. Importantly, inhibition of TGF-β signaling may have benefits in the treatment of the acute phase of autoimmune CNS inflammation.

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Section: Figuresupporting

confidence: 77%

Glia-dependent TGF-β signaling, acting independently of the TH17 pathway, is critical for initiation of murine autoimmune encephalomyelitis

Luo¹,

Ho²,

Buckwalter³

et al. 2007

J. Clin. Invest.

109

111

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show abstract

“…Many growth factors and neuroprotective substances, such as transforming growth factor-␤1 and glial cell-derived neurotrophic factor, show increased expression after brain insult (Humpel et al, 1994;Knuckey et al, 1996). This indicates that neuroprotective signals are transduced immediately after environmentally stressful conditions.…”

Section: Discussionmentioning

confidence: 90%

Overexpression of PrP^Cby Adenovirus-Mediated Gene Targeting Reduces Ischemic Injury in a Stroke Rat Model

Shyu¹,

Lin²,

Chiang³

et al. 2005

J. Neurosci.

116

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Prion diseases are induced by pathologically misfolded prion protein (PrPSc ), which recruit normal sialoglycoprotein PrP C by a templatedirected process. In this study, we investigated the expression of PrP C in a rat model of cerebral ischemia to more fully understand its physiological role. Immunohistochemical analysis demonstrated that PrP C -immunoreactive cells increased significantly in the penumbra of ischemic rat brain compared with the untreated brain. Western blot analysis showed that PrP C protein expression increased in ischemic brain tissue in a time-dependent manner. In addition, PrP C protein expression was seen to colocalize with neuron, glial, and vascular endothelial cells in the penumbric region of the ischemic brain. Overexpression of PrP C by injection of rAd (replication-defective recombinant adenoviral)-PGK (phosphoglycerate kinase)-PrP C -Flag into ischemic rat brain improved neurological behavior and reduced the volume of cerebral infarction, which is supportive of a role for PrP C in the neuroprotective adaptive cellular response to ischemic lesions. Concomitant upregulation of PrP C and activated extracellular signal-regulated kinase (ERK1/2) under hypoxia-reoxygenation in primary cortical cultures was shown to be dependent on ERK1/2 phosphorylation. During hypoxia-reoxygenation, mouse neuroblastoma cell line N18 cells transfected with luciferase rat PrP C promoter reporter constructs, containing the heat shock element (HSE), expressed higher luciferase activities (3-to 10-fold) than those cells transfected with constructs not containing HSE. We propose that HSTF-1 (hypoxia-activated transcription factor), phosphorylated by ERK1/2, may in turn interact with HSE in the promoter of PrP C resulting in gene expression of the prion gene. In summary, we conclude that upregulation of PrP C expression after cerebral ischemia and hypoxia exerts a neuroprotective effect on injured neural tissue. This study suggests that PrP C has physiological relevance to cerebral ischemic injury and could be useful as a therapeutic target for the treatment of cerebral ischemia.

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“…Some literature has indicated that expression of SN is upregulated after cerebral ischemic insult (7). Similarly, TGF-β1 and GDNF mRNA levels have also been shown to increase after brain injury (27,28). From this evidence, investigators have suggested that endogenous protective mechanisms could be activated after such insults (27,28).…”

Section: Discussionmentioning

confidence: 95%

Secretoneurin promotes neuroprotection and neuronal plasticity via the Jak2/Stat3 pathway in murine models of stroke

et al. 2008

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Differential neuronal and astrocytic expression of transforming growth factor beta isoforms in rat hippocampus following transient forebrain ischemia

Cited by 76 publications

References 60 publications

Glia-dependent TGF-β signaling, acting independently of the TH17 pathway, is critical for initiation of murine autoimmune encephalomyelitis

Glia-dependent TGF-β signaling, acting independently of the TH17 pathway, is critical for initiation of murine autoimmune encephalomyelitis

Overexpression of PrP^Cby Adenovirus-Mediated Gene Targeting Reduces Ischemic Injury in a Stroke Rat Model

Secretoneurin promotes neuroprotection and neuronal plasticity via the Jak2/Stat3 pathway in murine models of stroke

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Differential neuronal and astrocytic expression of transforming growth factor beta isoforms in rat hippocampus following transient forebrain ischemia

Cited by 76 publications

References 60 publications

Glia-dependent TGF-β signaling, acting independently of the TH17 pathway, is critical for initiation of murine autoimmune encephalomyelitis

Glia-dependent TGF-β signaling, acting independently of the TH17 pathway, is critical for initiation of murine autoimmune encephalomyelitis

Overexpression of PrPCby Adenovirus-Mediated Gene Targeting Reduces Ischemic Injury in a Stroke Rat Model

Secretoneurin promotes neuroprotection and neuronal plasticity via the Jak2/Stat3 pathway in murine models of stroke

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Overexpression of PrP^Cby Adenovirus-Mediated Gene Targeting Reduces Ischemic Injury in a Stroke Rat Model