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EGF and Stroke

Seyyed Mohyeddin Ziaee, Parisa Tabeshmehr, Khawaja Husnain Haider, Majidreza Farrokhi, Abdolhamid Shariat, Atena Amiri, Seyed Mojtaba Hosseini
BACKGROUND: Despite encouraging data in terms of neurological outcome, stem cell based therapy for ischemic stroke in experimental models and human patients is still hampered by multiple as yet un-optimized variables, i.e., time of intervention, that significantly influence the prognosis. The aim of the present study was to delineate the optimum time for neural stem cells (NSCs) transplantation after ischemic stroke. METHODS: The NSCs were isolated from 14 days embryo rat ganglion eminence and were cultured in NSA medium (neurobasal medium, 2% B27, 1% N2, bFGF 10 ng/mL, EGF 20 ng/mL and 1% pen/strep)...
2017: Stem Cell Investigation
Dominik Michalski, Roman Pitsch, Deepu R Pillai, Bianca Mages, Susanne Aleithe, Jens Grosche, Henrik Martens, Felix Schlachetzki, Wolfgang Härtig
Current stroke therapy is focused on recanalizing strategies, but neuroprotective co-treatments are still lacking. Modern concepts of the ischemia-affected neurovascular unit (NVU) and surrounding penumbra emphasize the complexity during the transition from initial damaging to regenerative processes. While early treatment with neurotrophic factors was shown to result in lesion size reduction and blood-brain barrier (BBB) stabilization, cellular consequences from these treatments are poorly understood. This study explored delayed cellular responses not only to ischemic stroke, but also to an early treatment with neurotrophic factors...
2017: PloS One
Su Jing Chan, Christopher Love, Myron Spector, Simon M Cool, Victor Nurcombe, Eng H Lo
Despite the efforts in developing therapeutics for stroke, recombinant tissue plasminogen activator (rtPA) remains the only FDA approved drug for ischemic stroke. Regenerative medicine targeting endogenous growth factors has drawn much interest in the clinical field as it provides potential restoration for the damaged brain tissue without being limited by a narrow therapeutic window. To date, most of the translational studies using regenerative medicines have encountered problems and failures. In this review, we discuss the effects of some trophic factors which include of erythropoietin (EPO), brain derived neurotrophic factor (BDNF), granulocyte-colony stimulating factor (G-CSF), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), epidermal growth factor (EGF) and heparin binding epidermal growth factor (HB-EGF) in experimental ischemic stroke models and elaborate the lost in translation of the candidate growth factors from bench to bedside...
July 2017: Neurochemistry International
Neven Maksemous, Robert A Smith, Larisa M Haupt, Lyn R Griffiths
BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic, hereditary, small vessel disease of the brain causing stroke and vascular dementia in adults. CADASIL has previously been shown to be caused by varying mutations in the NOTCH3 gene. The disorder is often misdiagnosed due to its significant clinical heterogeneic manifestation with familial hemiplegic migraine and several ataxia disorders as well as the location of the currently identified causative mutations...
November 24, 2016: Human Genomics
Svetlana Demyanenko, Anatoly Uzdensky
In ischemic stroke, cell damage propagates from infarct core to surrounding tissue. To reveal proteins involved in neurodegeneration and neuroprotection, we explored the protein profile in penumbra surrounding the photothrombotic infarct core induced in rat cerebral cortex by local laser irradiation after Bengal Rose administration. Using antibody microarrays, we studied changes in expression of 224 signaling proteins 1, 4, or 24 h after photothrombotic infarct compared with untreated contralateral cortex...
October 22, 2016: Molecular Neurobiology
N Subirós, H Pérez-Saad, L Aldana, C L Gibson, W S Borgnakke, D Garcia-Del-Barco
BACKGROUND: Combined therapy with epidermal growth factor (EGF) and growth hormone-releasing peptide 6 (GHRP-6) in stroke models has accumulated evidence of neuroprotective effects from several studies, but needs further support before clinical translation. Comparing EGF + GHRP-6 to hypothermia, a gold neuroprotection standard, may contribute to this purpose. OBJECTIVES: The aims of this study were to compare the neuroprotective effects of a combined therapy based on EGF + GHRP-6 with hypothermia in animal models of (a) global ischemia representing myocardial infarction and (b) focal brain ischemia representing ischemic stroke...
November 2016: Neurological Research
Shen-Zhong Qiu, Hong-Xiang Wang, Jia Shen, Guan-Rong Zheng, Bin Chen, Jian-Jun Huang, Jian-Bo Gao
BACKGROUND: Signal peptide-Cub-Epidermal growth factor domain-containing protein 1 (SCUBE1) in peripheral blood, which is identified as a marker for coagulation, was reported to be an independent predictor of poor outcome in some illnesses. We investigated the clinical utility of serum SCUBE1 in the prognosis of intracerebral hemorrhage (ICH). METHODS: A total of 128 consecutive patients, admitted to emergency service due to acute ICH, and 128 healthy individuals were included in this prospective study...
October 1, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
Carmen Capone, Fabrice Dabertrand, Celine Baron-Menguy, Athena Chalaris, Lamia Ghezali, Valérie Domenga-Denier, Stefanie Schmidt, Clément Huneau, Stefan Rose-John, Mark T Nelson, Anne Joutel
Cerebral small vessel disease (SVD) is a leading cause of stroke and dementia. CADASIL, an inherited SVD, alters cerebral artery function, compromising blood flow to the working brain. TIMP3 (tissue inhibitor of metalloproteinase 3) accumulation in the vascular extracellular matrix in CADASIL is a key contributor to cerebrovascular dysfunction. However, the linkage between elevated TIMP3 and compromised cerebral blood flow (CBF) remains unknown. Here, we show that TIMP3 acts through inhibition of the metalloprotease ADAM17 and HB-EGF to regulate cerebral arterial tone and blood flow responses...
August 1, 2016: ELife
Seyed Mojtaba Hosseini, Mohammad Farahmandnia, Sepehr Kazemi, Benafshe Shakibajahromi, Fatemeh Sabet Sarvestani, Zahra Khodabande
BACKGROUND: Nowadays, stroke leads to a significant part of the adult mortality and morbidity and also it could result in some neurological deficits in the patients' lives. Cell therapy has opened a new approach to treat the brain ischemia and reduce its terrible effects on the patients' lives. There are several articles which show that the cell therapy could be beneficial for treating brain stroke. In this study, we have planned to present a new cell therapy method for stroke by administration of Mesenchymal stem cells and differentiated neural stem cells without astrocytes...
November 2015: International Journal of Stem Cells
Mi Wang, Yong-Bo Tang, Ming-Ming Ma, Jing-Hui Chen, Chang-Ping Hu, Shui-Ping Zhao, Dao-Quan Peng, Jia-Guo Zhou, Yong-Yuan Guan, Zheng Zhang
AIMS: Ionic perturbation in vascular smooth muscle cells contributes to cerebrovascular remodelling in the setting of hypertension, but the role of transient receptor potential (TRP) channel superfamily remains unknown. The present study was conducted to define the contribution of TRP channels to cerebrovascular remodelling. METHODS AND RESULTS: By integrating quantitative PCR, western blotting, patch clamping, and Ca(2+) imaging, we identified TRP channel, subfamily canonical, member 3 (TRPC3) as the channel subtype most considerably elevated in basilar arteries of two-kidney, two-clip stroke-prone hypertensive rats...
January 1, 2016: Cardiovascular Research
Nelvys Subirós, Héctor M Pérez-Saad, Jorge A Berlanga, Lizet Aldana, Gerardo García-Illera, Claire L Gibson, Diana García-Del-Barco
BACKGROUND: Stroke continues to be a leading cause of mortality and morbidity worldwide, and novel therapeutic options for ischaemic stroke are urgently needed. In this context, drug combination therapies seem to be a viable approach, which has not been fully explored in preclinical studies. OBJECTIVES: In this work, we assessed the dose-response relationship and therapeutic time window, in global brain ischaemia, of a combined therapeutic approach of recombinant human epidermal growth factor (EGF) and growth hormone-releasing peptide-6 (GHRP-6)...
March 2016: Neurological Research
Conor Best, Heidi Struthers, Erin Laciny, Michael Royal, Dominic N Reeds, Kevin E Yarasheski
CONTEXT: HIV infection is associated with a greater risk for fasting hyperinsulinemia, impaired glucose tolerance, and higher incidence rates for vascular disease, myocardial infarction, or stroke despite effective combination antiretroviral therapy (cART). The underlying mechanism(s) may involve chronic low-grade systemic inflammation and immune cell activation. Dipeptidyl peptidase-4 inhibitors (sitagliptin) improve glucose tolerance and may possess immunomodulatory effects because leukocyte CD26 cell surface receptors express dipeptidyl peptidase-4 activity...
July 2015: Journal of Clinical Endocrinology and Metabolism
Cletus Cheyuo, Monowar Aziz, Weng-Lang Yang, Asha Jacob, Mian Zhou, Ping Wang
The mediators in activating neural stem cells during the regenerative process of neurogenesis following stroke have not been fully identified. Milk fat globule-EGF Factor VIII (MFG-E8), a secreted glycoprotein serves several cellular functions by binding to its receptor, αv β3-integrin. However, its role in regulating neural stem cells after stroke has not been determined yet. We therefore, aim to reveal whether MFG-E8 promotes neural stem cell proliferation and migration during stroke. Stroke was induced in wild-type (Wt) and MFG-E8-deficinet (Mfge8-/-) mice by transient middle cerebral artery occlusion (tMCAO)...
2015: PloS One
Rasha H Alghamdi, Paul O'Reilly, Chunyu Lu, James Gomes, Thomas A Lagace, Ajoy Basak
BACKGROUND: High level of Low Density Lipoprotein-Cholesterol (LDL-C) in circulation in the blood is associated with an elevated risk of cardiovascular disease (CVD) and stroke. Currently the statin drugs which inhibit the enzyme HMG-CoA reductase responsible for cholesterol synthesis in the liver are very effective in lowering LDL-cholesterol. However these drugs are often associated with serious side effects particularly for ∼10-12% of cases. Therefore there is a need to develop non-statin based cholesterol reducing agents...
March 6, 2015: European Journal of Medicinal Chemistry
Suha Turkmen, Umut Eryigit, Yunus Karaca, Ahmet Mentese, Uzun Aysegul Sumer, Esin Yulug, Nurhak Aksut, Sibel Gazioglu, Abdulkadir Gunduz
OBJECTIVES: This study was intended to examine possible diagnostic value of plasma Signal Peptide-Cub-Egf domain-containing protein-1 (SCUBE1) levels in an experimental model of acute ischemic stroke. METHODS: Twenty-four female Sprague Dawley rats were divided into four groups. Blood and brain tissue specimens were collected immediately following artery ligation (control; Group 1), 1h after ligation (Group 2), 2 h after ligation (Group 3) and 6h after ligation (Group 4)...
February 2015: American Journal of Emergency Medicine
Silvia Bianchi, Enza Zicari, Alessandra Carluccio, Ilaria Di Donato, Francesca Pescini, Serena Nannucci, Raffaella Valenti, Michele Ragno, Domenico Inzitari, Leonardo Pantoni, Antonio Federico, Maria Teresa Dotti
The objective of the study is to detail clinical and NOTCH3 gene mutational spectrum in a large group of Italian CADASIL patients. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a familial cerebral small vessels disease caused by mutations in the NOTCH3 gene on 19p13 usually presenting in young or middle adulthood. Characteristic features include migraine, recurrent lacunar stroke, subcortical dementia, mood disturbances and leukoencephalopathy. The disorder is often overlooked and misdiagnosed...
January 2015: Journal of Neurology
Fei Liu, Qin Hu, Bo Li, Anatol Manaenko, Yujie Chen, Junjia Tang, Zongduo Guo, Jiping Tang, John H Zhang
BACKGROUND AND PURPOSE: Milk fat globule-EGF factor-8 (MFGE8) has been reported to be neuroprotective in ischemic stroke. However, the effects of MFGE8 in early brain injury after subarachnoid hemorrhage (SAH) have not been investigated. We investigated the role of MFGE8 in early brain injury and the potential mechanisms in antioxidation after SAH. METHODS: Two dosages (1 μg and 3.3 μg) of recombinant human MFGE8 were injected intracerebroventricularly at 1.5 hours after SAH...
December 2014: Stroke; a Journal of Cerebral Circulation
Lorena Mosca, Francesca Rivieri, Raffaella Tanel, Aldo Bonfante, Alessandro Burlina, Emanuela Manfredini, Paola Primignani, Giovanni P Gesu, Alessandro Marocchi, Silvana Penco
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an adult onset hereditary vascular disease with neurological manifestations. The classical clinical course is relentlessly progressive with early transient ischaemic attacks (TIA) or strokes, dementia and finally death in the mid-1960s. The disorder is inherited in an autosomal dominant fashion, with high penetrance and broad variable clinical course even within family. It is caused by mutations in the NOTCH3 gene; all causative mutations result in gain or loss of a cysteine residue within the extracellular domain, with exons 3 and 4 reported as hot spot mutational sites...
December 2014: Journal of Molecular Neuroscience: MN
Velidi H Rao, Vikash Kansal, Samantha Stoupa, Devendra K Agrawal
Mechanisms underlying the rupture of atherosclerotic plaque, a crucial factor in the development of myocardial infarction and stroke, are not well defined. Here, we examined the role of epidermal growth factor (EGF)-mediated matrix metalloproteinases (MMP) on the stability of interstitial collagens in vascular smooth muscle cells (VSMCs) isolated from carotid endarterectomy tissues of symptomatic and asymptomatic patients with carotid stenosis. VSMCs isolated from the carotid plaques of both asymptomatic and symptomatic patients were treated with EGF...
February 1, 2014: Physiological Reports
Chikara Ueyama, Hideki Horibe, Tetsuo Fujimaki, Mitsutoshi Oguri, Kimihiko Kato, Yoshiji Yamada
Findings of previous studies demonstrated that rs6007897 (C→T, Ala2268Thr) of the cadherin, epidermal growth factor (EGF) laminin A G-type repeats (LAG) seven-pass G-type receptor 1 gene (CELSR1) and rs9846911 (A→G) at chromosome 3q28 were significantly associated with ischemic stroke and chronic kidney disease, respectively. Given that hypertension is a risk factor for both ischemic stroke and chronic kidney disease, it was hypothesized that the association of rs6007897 with ischemic stroke or of rs9846911 with chronic kidney disease might be attributable, at least in part, to their effects on genetic susceptibility to hypertension...
November 2013: Biomedical Reports
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