Induction of transforming growth factor beta receptors following focal ischemia in the rat brain (original) (raw)
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Acta Neuropathologica, 1999
Transforming growth factor beta (TGF-β) is involved in the modulation of cell growth, differentiation and repair following injury of various organs. Previous studies on human autopsy material have indicated that TGF-β isoforms-β1,-β2 and-β3, and TGF-β receptor type I are expressed in various cells of necrotizing brain lesions like infarction and abscess. The present immunohistochemical study was designed to investigate changes that may occur with regard to TGF-β and its receptors type I and II in a rat model of focal brain ischemia induced by transient or permanent occlusion of the middle cerebral artery. Our findings indicate that at days 1 and 3 following such transient and permanent ischemia there is an up-regulation of TGF-β isoforms-β1,-β2 and-β3, and TGF-β receptor types I and II mainly in the perifocal neurons, reactive astroglial cells, endothelial cells and macrophages.
Transforming growth factor-β1 exhibits delayed gene expression following focal cerebral ischemia
Brain Research Bulletin, 1995
Transfmlning growth factor-~l (TGF-pl) is a pleiotropic peptide growth factor. The expression of TGF-pl mRNA in the focal ~ cortex of rats was studied by means of Nornw, h,~xk~tim. A modmt~ k)w k,~ of c(mt~,v~ expressed TGF-~I1 mRNA was det~tml following sham-surgery or in the co.;iidalafal (nmgschemic) cortex. A idgnifi~nt inoremm of TGF-/ll mRNA Iovel in the ischemic cortox was ob-~ed at 2 days (&2-tokl k.:me~ =~.pared to dmn-opormd animlds, p < 0.01, n = 4) folBowing permanent occlusion of Ule middle cerebral artmy (PMCAO). The elevabld TGF~I1 mRNA expression was plateaued for up to 15 days (3.6-told increase, p < 0.01) following PMCAO. This m profile for TGF-~I mRNA exlxeasion in focal stroke was signiflcanUy delayed compared to that of TNF-a, IL-lp and IL-6 mRNA eXlXassions as demonslbrated prevlomdy which peaked at 12 h and deceeased to aknost basa lewas by S dws falowing PMeAO. Wcmmnngly. the TGF-,81 mRNA exlx'oeaton profile was mmmtudl~ parallel with that of monocyte/~ a~:tamdation in the ischemic cortex, as well as with the increased formation of exll~-ceUular matdx in the focal ischemtc bra~ Thase data suggast that TGF-/I1 may ptay a role in anti-inflammatory process and in tissue remodeling following ischemic brain injury.
Transforming growth factor-β and ischemic brain injury
2003
1. Necrosis and apoptosis are the two fundamental hallmarks of neuronal death in stroke. Nevertheless, thrombolysis, by using the recombinant serine protease t-PA, remains until now the only approved treatment of stroke in man.
Journal of Cerebral Blood Flow & Metabolism, 1999
Transforming growth factor-α (TGF-α) is a ligand for the epidermal growth factor (EGF) receptor (EGFR), and is more abundant than EGF in the brain. The authors studied whether administration of exogenous TGF-α into the brain can protect neurons against ischemia in a model of permanent middle cerebral artery (MCA) occlusion in the rat, and whether any effect of TGF-α was mediated by EGFR by administering 4,5-dianilinophthalimide (DAPH), a protein-tyrosine kinase inhibitor with high selectivity for EGFR. Rats received either TGF-α (10 or 25 ng), DAPH (100 ng), DAPH plus TGF-α (25 ng), or vehicle in the ipsilateral first ventricle. Drugs were administered twice: 30 minutes before and 30 minutes after MCA occlusion, and infarct volume was evaluated 24 hours later. Transforming growth factor-α at the dose of 25 ng caused a statistically significant reduction of infarct volume (60%) in relation to ischemic rats administered vehicle. This reduction was no longer seen when TGF-α was adminis...
Transforming Growth Factor Beta (TGFβ) was a major regulatory molecule to suppress the immune response in the inflammatory process. TGFβ was also a growth factor that affects growth, homeostasis, angiogenesis and tissue repair. In the acute phase of stroke, astrocytes were activated and the cells were able to produce anti-inflammatory cytokines such as TGFβ. The purpose of this study was to determine whether there is a correlation between serum levels of TGFβ at acute phase of ischemic stroke and patients' clinical outcomes. The study was conducted in patients with acute anterior system ischemic stroke who came to Siloam Hospital in Tangerang, Indonesia. Blood samples were taken to measure the levels of TGFβ-1serum at ≤ 72 hours and the 3 rd day of onset. Clinical severity of stroke assessed using the National Institute of Health (NIH) Stroke Scale at 72 hours, 7 th days and 30 th days after stroke. The mean serum levels of TGFβ-1 at ≤ 72 hours in the group of subjects with mild NIH Stroke Scale degree was higher than in the group of subjects with moderate/severe NIH Stroke Scale degree (p = 0.046). The subjects with elevated levels of TGF-β1 in the acute phase of stroke had better clinical degrees at the 30 th day after the stroke, although statistically was not significant (p = 0.241). Result of this study showed that TGFβ-1 may act as a neuroprotector against brain tissue damage after ischemic stroke.
Transforming growth factor α induces angiogenesis and neurogenesis following stroke
Neuroscience, 2009
The cytokine transforming growth factor α (TGFα) has proangiogenic and proneurogenic effects and can potentially reduce infarct volumes. Therefore, we administered TGFα or vehicle directly into the area surrounding the infarct in female mice that received gender-mismatched bone marrow transplants from GFP-expressing males prior to undergoing permanent middle cerebral artery occlusion. Newborn cells were tracked with BrdU labeling and immunohistochemistry at 90 days after stroke onset. We also studied the ingress of bone marrow derived cells into the ischemic brain to determine whether such cells contribute to angiogenesis or neurogenesis. Infarct volumes were measured at 90 days post stroke. The results show that TGFα led to significant increments in the number of newborn neurons and glia in the ischemic hemisphere. TGFα also led to significant increments in the number of bone marrow derived cells entering into the ischemic hemisphere. Most of these cells did not label with BrdU and represented endothelial cells that incorporated into blood vessels in the infarct border zone. Our results also show that infarct size was significantly reduced in animals treated with TGFα compared with controls. These results suggest that TGFα can induce angiogenesis, neurogenesis and neuroprotection after stroke. At least part of the pro-angiogenic effect appears to be secondary to the incorporation of bone marrow derived endothelial cells into blood vessels in the infarct border zone.
Journal of Cerebral Blood Flow & Metabolism, 2001
Growth factors promote cell growth and survival and protect the brain from developing injury after ischemia. In this article, the authors examined whether transforming growth factor-α (TGF-α) was protective in transient focal ischemia and whether alteration of cerebral circulation was involved. Rats received intraventricular TGF-α (50 ng, either split into 2 doses given 30 minutes before and 30 minutes after middle cerebral artery occlusion (MCAO), or 1 dose given 30 minutes after MCAO) or vehicle. Rats were subjected to 1-hour intraluminal MCAO and cerebral blood flow was recorded continuously by laser–Doppler flowmetry. Infarct volume was measured 1 and 4 days later. The effects of TGF-α on arterial tone were assessed in isolated rabbit basilar and common carotid arteries. Transforming growth factor-α before and after ischemia reduced infarct volume by 70% at 1 day and 50% at 4 days. Transforming growth factor-α given only after ischemia also did reduce infarct volume by 70% at 1 ...
Journal of Cerebral Blood Flow & Metabolism, 2001
Growth factors promote cell growth and survival and protect the brain from developing injury after ischemia. In this article, the authors examined whether transforming growth factor-α (TGF-α) was protective in transient focal ischemia and whether alteration of cerebral circulation was involved. Rats received intraventricular TGF-α (50 ng, either split into 2 doses given 30 minutes before and 30 minutes after middle cerebral artery occlusion (MCAO), or 1 dose given 30 minutes after MCAO) or vehicle. Rats were subjected to 1-hour intraluminal MCAO and cerebral blood flow was recorded continuously by laser–Doppler flowmetry. Infarct volume was measured 1 and 4 days later. The effects of TGF-α on arterial tone were assessed in isolated rabbit basilar and common carotid arteries. Transforming growth factor-α before and after ischemia reduced infarct volume by 70% at 1 day and 50% at 4 days. Transforming growth factor-α given only after ischemia also did reduce infarct volume by 70% at 1 ...