Expression of cytokines in rat brain with focal cerebral ischemia after grafting with bone marrow stromal cells and endothelial progenitor cells

He, Xiaofu; Chen, Zhenzhou; Cai, Yuchen; Xu, Gang; Shang, Jiang-Hua; Kou, Sheng-Bing; Li, Ming; Zhang, Hongtian; Duan, Chuan‐Zhi; Zhang, Shizhong; Ke, Yiquan; Zeng, Yanjun; Xu, Ran; Jiang, Xiao-dan

doi:10.3109/14653249.2010.510505

Cited by 31 publications

(21 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the current study, while SCO downregulated VEGF, BDNF, NGF, and CREB, transplantation of EPCs exerted neuroprotective actions, at least partly, via boosting their hippocampal levels. Mounting evidence has indicated that EPCs release cytokines and growth factors including VEGF and BDNF that confer protection against ischemic axonal degeneration and promote neuronal survival [25,44]. This was further supported by the rescuing effects of EPCs-conditioned media which contained secreted trophic factors on the axonal degeneration provoked by oxygenglucose deprivation [25].…”

Section: Discussionmentioning

confidence: 96%

Bone Marrow-Derived Endothelial Progenitor Cells Protect Against Scopolamine-Induced Alzheimer-Like Pathological Aberrations

et al. 2014

View full text Add to dashboard Cite

Vascular endothelial dysfunction plays a key role in the pathogenesis of Alzheimer's disease (AD). Patients with AD have displayed decreased circulating endothelial progenitor cells (EPCs) which repair and maintain the endothelial function. Transplantation of EPCs has emerged as a promising approach for the management of cerebrovascular diseases including ischemic stroke, however, its impact on AD has been poorly described. Thus, the current study aimed at investigating the effects of bone marrow-derived (BM) EPCs transplantation in repeated scopolamine-induced cognitive impairment, an experimental model that replicates biomarkers of AD. Intravenously transplanted BM-EPCs migrated into the brain of rats and improved the learning and memory deficits. Meanwhile, they mitigated the deposition of amyloid plaques and associated histopathological alterations. At the molecular levels, BM-EPCs blunted the increase of hippocampal amyloid beta protein (Aβ), amyloid precursor protein (APP) and reinstated the Aβ-degrading neprilysin together with downregulation of p-tau and its upstream glycogen synthase kinase-3β (GSK-3β). They also corrected the perturbations of neurotransmitter levels including restoration of acetylcholine and associated esterase along with dopamine, GABA, and the neuroexitatory glutamate. Furthermore, BM-EPCs induced behavioral recovery via boosting of vascular endothelial growth factor (VEGF), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and its upstream cAMP response element binding (CREB), suppression of the proinflammatory tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and upregulation of interleukin-10 (IL-10). BM-EPCs also augmented Nrf2 and seladin-1. Generally, these actions were analogous to those exerted by adipose tissue-derived mesenchymal stem cells (AT-MSCs) and the reference anti-Alzheimer donepezil. For the first time, these findings highlight the beneficial actions of BM-EPCs against the memory deficits and AD-like pathological dysfunction.

show abstract

Section: Discussionmentioning

confidence: 96%

Bone Marrow-Derived Endothelial Progenitor Cells Protect Against Scopolamine-Induced Alzheimer-Like Pathological Aberrations

et al. 2014

View full text Add to dashboard Cite

show abstract

“…These include but are not limited to vascular endothelial growth factor, stromal cell-derived factor 1a (SDF-1a), basic fibroblast growth factor, brain-derived neurotrophic factor. 25,30,31 Our data indicate that EPCs can be exploited to provide survival cues to axons after ischemic but not mechanical injury. One reason for this difference in response may be related to the severity of injury incurred through mechanical trauma in relation to ischemic injury.…”

Section: Discussionmentioning

confidence: 99%

Bone Marrow-Derived Endothelial Progenitor Cells Protect Postischemic Axons after Traumatic Brain Injury

Park

Liu

et al. 2013

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

White matter sparing after traumatic brain injury (TBI) is an important predictor of survival and outcome. Blood vessels and axons are intimately associated anatomically and developmentally. Neural input is required for appropriate vascular patterning, and vascular signaling is important for neuron development and axon growth. Owing to this codependence between endothelial cells and axons during development and the contribution of endothelial progenitor cells (EPCs) in ischemic injury, we hypothesized that EPCs are important in axonal survival after TBI. We examined the effects of allogenic-cultured EPCs on white matter protection and microvascular maintenance after midline fluid percussion injury in adult Sprague-Dawley rats. We used two in vitro models of injury, mechanical stretch and oxygen-glucose deprivation (OGD), to examine the effects of EPCs on the mechanical and ischemic components of brain trauma, respectively. Our results indicate that EPCs improve the white matter integrity and decrease capillary breakdown after injury. Cultured cortical neurons exposed to OGD had less axon degeneration when treated with EPC-conditioned media, whereas no effect was seen in axons injured by mechanical stretch. The results indicate that EPCs are important for the protection of the white matter after trauma and represent a potential avenue for therapy.

show abstract

“…11 Transplanted EPCs are capable of secreting proangiogenic factors, such as VEGF. 21 Previous studies have reported that acute VEGF therapy (days 1-3) aggravates ischemic injury because of the increased blood-brain barrier leakage and hemorrhage formation; however, in the subacute stage of cerebral ischemia (days 7-21), increased VEGF contributes to favorable stabilization and maturation of neovessels. 22 In our study, the increased VEGF may be caused mostly by EPCs and may exert a positive effect.…”

Section: Discussionmentioning

confidence: 99%

Synergistic Effects of Transplanted Endothelial Progenitor Cells and RWJ 67657 in Diabetic Ischemic Stroke Models

Bai

Wang

Chen

et al. 2015

Stroke

View full text Add to dashboard Cite

Background and Purpose— An immature vascular phenotype in diabetes mellitus may cause more severe vascular damage and poorer functional outcomes after stroke, and it would be feasible to repair damaged functional vessels using endothelial progenitor cell (EPC) transplantation. However, high glucose induces p38 mitogen-activated protein kinase activation, which can accelerate the senescence and apoptosis of EPCs. The aim of this study was to investigate the combined effects of EPC transplantation and p38 mitogen-activated protein kinase inhibitor administration on diabetic stroke outcomes. Methods— Bone marrow–derived EPCs were injected intra-arterially into db/db mice after ischemic stroke induction. RWJ 67657 (RWJ), a p38 mitogen-activated protein kinase inhibitor, was administered orally for 7 consecutive days, with the first dose given 30 minutes before stroke induction. Functional outcome was determined at days 0, 1, 7, 14, and 21. Angiogenesis, neurogenesis, infarct volume, and Western blotting assays were performed on day 7, and white matter remodeling was determined on day 14. Results— Neither EPC transplantation nor RWJ administration alone significantly improved diabetic stroke outcome although RWJ displayed a potent anti-inflammatory effect. By both improving the functioning of EPCs and reducing inflammation, EPC transplantation plus RWJ administration in vivo synergistically promoted angiogenesis and neurogenesis after diabetic stroke. In addition, the white matter remodeling, behavioral scores, and expressions of vascular endothelial growth factor and brain-derived neurotrophic factor were significantly increased in diabetic mice treated with both EPCs and RWJ. Conclusions— The combination of EPC transplantation and RWJ administration accelerated recovery from diabetic stroke, which might have been caused by increased levels of proangiogenic and neurotrophic factors.

show abstract

Expression of cytokines in rat brain with focal cerebral ischemia after grafting with bone marrow stromal cells and endothelial progenitor cells

Cited by 31 publications

References 20 publications

Bone Marrow-Derived Endothelial Progenitor Cells Protect Against Scopolamine-Induced Alzheimer-Like Pathological Aberrations

Bone Marrow-Derived Endothelial Progenitor Cells Protect Against Scopolamine-Induced Alzheimer-Like Pathological Aberrations

Bone Marrow-Derived Endothelial Progenitor Cells Protect Postischemic Axons after Traumatic Brain Injury

Synergistic Effects of Transplanted Endothelial Progenitor Cells and RWJ 67657 in Diabetic Ischemic Stroke Models

Contact Info

Product

Resources

About