Treatment of Stroke With Erythropoietin Enhances Neurogenesis and Angiogenesis and Improves Neurological Function in Rats
TLDR
The data suggest that EPO-increased VEGF and BDNF may be involved in angiogenesis and neurogenesis, which could contribute to functional recovery.Abstract:
Background and Purpose— Erythropoietin (EPO) promotes proliferation and differentiation of erythroid progenitors and the survival of maturing erythroid cells. Here, we investigated the role of EPO in brain repair after stroke. Methods— Rats were treated with recombinant human EPO (rhEPO) at 24 hours after the onset of embolic stroke. An array of behavior tests was performed. Rats were euthanized 28 days after stroke for measurements of infarct volume, angiogenesis, and neurogenesis. In vitro, neurospheres derived from the subventricular zone (SVZ) of the rat and cerebral endothelial cells derived from the mouse were treated with rhEPO. Capillary-like tube formation and neuronal differentiation were measured. Results— Treatment with rhEPO significantly improved functional recovery, along with increases in density of cerebral microvessels at the stroke boundary and numbers of BrdU, doublecortin, and nestin immunoreactive cells in the SVZ. rhEPO treatment significantly increased brain levels of vascular endo...read more
Citations
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The Science of Stroke: Mechanisms in Search of Treatments
TL;DR: This review focuses on mechanisms and emerging concepts that drive the science of stroke in a therapeutic direction and poses a number of fundamental questions that may generate new directions for research and possibly new treatments that could reduce the impact of this enormous economic and societal burden.
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A Neurovascular Niche for Neurogenesis after Stroke
TL;DR: A novel brain environment for neuronal regeneration after stroke is defined and molecular mechanisms that are shared between angiogenesis and neurogenesis during functional recovery from brain injury are identified.
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Persistent production of neurons from adult brain stem cells during recovery after stroke
Pär Thored,Andreas Arvidsson,Emanuele Cacci,Henrik Ahlenius,Therése Kallur,Vladimer Darsalia,Christine T. Ekdahl,Zaal Kokaia,Olle Lindvall +8 more
TL;DR: It is shown that endogenous neural stem cells continuously supply the injured adult brain with new neurons, which suggests novel self‐repair strategies to improve recovery after stroke.
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Neurorestorative therapies for stroke: underlying mechanisms and translation to the clinic
TL;DR: The molecular pathways activated by these therapies, which induce remodelling of the injured brain via angiogenesis, neurogenesis, and axonal and dendritic plasticity, are discussed, may help with translation of restorative therapy from the laboratory to the clinic.
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Preconditioning and tolerance against cerebral ischaemia: from experimental strategies to clinical use
TL;DR: Whether preconditioning and tolerance occur naturally in the brain and the most promising candidate strategies that are being investigated are discussed and the clinical situations that might benefit from such procedures are discussed.
References
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Journal ArticleDOI
Vascular niche for adult hippocampal neurogenesis.
TL;DR: The present data provide the first evidence that adult neurogenesis occurs within an angiogenic niche and may provide a novel interface where mesenchyme‐derived cells and circulating factors influence plasticity in the adult central nervous system.
Journal ArticleDOI
Neural stem cells in the adult mammalian forebrain: a relatively quiescent subpopulation of subependymal cells
Cindi M. Morshead,Brent A. Reynolds,Constance Craig,Michael W. McBurney,William A. Staines,Dante J. Morassutti,Samuel Weiss,Derek van der Kooy +7 more
TL;DR: In vitro formation of clonally derived spheres of cells that exhibit stem cell properties such as self-maintenance and the generation of a large number of progeny comprising the major cell types found in the central nervous system suggest that a relatively quiescent subependymal cell is the in vivo source of neural stem cells.
Journal ArticleDOI
Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo
TL;DR: Findings implicate the angiogenesis factor VEGF in neurogenesis as well in murine cerebral cortical cultures and in adult rat brain in vivo.
Journal ArticleDOI
VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain
Zheng Gang Zhang,Li Zhang,Quan Jiang,Ruilan Zhang,Kenneth Davies,Cecylia Powers,Nicholas van Bruggen,Michael Chopp +7 more
TL;DR: VEGF can markedly enhance angiogenesis in the ischemic brain and reduce neurological deficits during stroke recovery and that inhibition of VEGF at the acute stage of stroke may reduce the BBB permeability and the risk of hemorrhagic transformation after focal cerebral ischemia.
Journal ArticleDOI
Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress
Anna-Leena Sirén,Maddalena Fratelli,Michael Brines,Christoph G. Goemans,Simona Casagrande,Piotr Lewczuk,Sonja Keenan,Christoph H. Gleiter,Claudio Pasquali,Annalisa Capobianco,Tiziana Mennini,Rolf Heumann,Anthony Cerami,Hannelore Ehrenreich,Pietro Ghezzi +14 more
TL;DR: Data suggest that inhibition of neuronal apoptosis underlies short latency protective effects of EPO after cerebral ischemia and other brain injuries, and the neurotrophic actions suggest there may be longer-latency effects as well.
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