Erythropoietin Dampens Injury-Induced Microglial Motility

Mitkovski, Mišo; Dahm, Liane; Heinrich, Ralf; Monnheimer, Mathieu; Gerhart, Simone; Stegmüller, Judith; Hanisch, Uwe‐Karsten; Nave, Klaus‐Armin; Ehrenreich, Hannelore

doi:10.1038/jcbfm.2015.100

Cited by 13 publications

(10 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The preparation and culture conditions of primary mouse oligodendrocytes and microglia are described in detail elsewhere (24)(25). In brief, oligodendrocytes were prepared from the forebrains of newborn P1-2 NMRI mice.…”

Section: Cell Culturementioning

confidence: 99%

“…In addition, EPO and EPOR mRNA are expressed in brain tissue (21), and specific binding sites for EPO in the brain have been demonstrated in mouse and humans by means of radiolabeled EPO (22)(23). In cell culture, mRNA expression combined with functional assays, for example, altered phosphorylation of second messenger pathways induced by EPO in microglia, served to prove specific EPOR expression in the absence of reliable EPOR-AB (24).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Widespread Expression of Erythropoietin Receptor in Brain and Its Induction by Injury

Ott

Martens²,

Hassouna

et al. 2015

Mol Med

Self Cite

View full text Add to dashboard Cite

Section: Cell Culturementioning

confidence: 99%

mentioning

confidence: 99%

Widespread Expression of Erythropoietin Receptor in Brain and Its Induction by Injury

Ott

Martens²,

Hassouna

et al. 2015

Mol Med

Self Cite

View full text Add to dashboard Cite

“…Iba-1 immunostatining is classically used to label microglia, however, we only analyzed microglia burden and it is possible that more complex inflammatory changes are not covered with our approach. Previous studies have shown that microglia express EPO receptors (Nagai et al, 2001) and that EPO may reduce motility, as an important feature of microglial pathological reaction to damage (Mitkovski et al, 2015), while promoting the polarization of microglia toward the protective M2 phenotype (Wei et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Erythropoietin Improves Atrophy, Bleeding and Cognition in the Newborn Intraventricular Hemorrhage

Hierro-Bujalance

Infante-Garcia

Sanchez-Sotano

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

The germinal matrix-intraventricular hemorrhage (GM-IVH) is one of the most devastating complications of prematurity. The short-and long-term neurodevelopmental consequences after severe GM-IVH are a major concern for neonatologists. These kids are at high risk of psychomotor alterations and cerebral palsy; however, therapeutic approaches are limited. Erythropoietin (EPO) has been previously used to treat several central nervous system complications due to its role in angiogenesis, neurogenesis and as growth factor. In addition, EPO is regularly used to reduce the number of transfusions in the preterm infant. Moreover, EPO crosses the blood-brain barrier and EPO receptors are expressed in the human brain throughout development. To analyze the role of EPO in the GM-IVH, we have administered intraventricular collagenase (Col) to P7 mice, as a model of GM-IVH of the preterm infant. After EPO treatment, we have characterized our animals in the short (14 days) and the long (70 days) term. In our hands, EPO treatment significantly limited brain atrophy and ventricle enlargement. EPO also restored neuronal density and ameliorated dendritic spine loss. Likewise, inflammation and small vessel bleeding were also reduced, resulting in the preservation of learning and memory abilities. Moreover, plasma gelsolin levels, as a feasible peripheral marker of GM-IVHinduced damage, recovered after EPO treatment. Altogether, our data support the positive effect of EPO treatment in our preclinical model of GM-IVH, both in the short and the long term.

show abstract

“…Prominent general functions of Epo in the nervous system and in other non-hematopoietic tissues are protection from apoptosis, reduction of inflammatory responses and re-establishment of compromised functions by support of proliferation, migration and differentiation to compensate for lost or injured cells [ 12 ]. Concerning the nervous system more specifically, Epo has been demonstrated to be crucial for normal brain development [ 30 , 31 ], to act neuroprotectively after hypoxic/ischemic insults and glutamate excitotoxicity [ 28 , 32 ], to suppress neuroinflammatory processes including activation of microglia [ 33 , 34 ] and to promote regeneration after axonal damage [ 35 , 36 , 37 ]. Moreover, Epo enhanced cognitive performance and memory retrieval in healthy humans and patients affected by mood disorders or schizophrenia [ 38 , 39 , 40 , 41 , 42 , 43 ] paralleling experimental observations of wild type rodents, rodent models for neuropsychiatric diseases and diabetic mice [ 44 , 45 , 46 , 47 ].…”

Section: Introductionmentioning

confidence: 99%

Alternative Erythropoietin Receptors in the Nervous System

Ostrowski

Heinrich

2018

JCM

Self Cite

View full text Add to dashboard Cite

In addition to its regulatory function in the formation of red blood cells (erythropoiesis) in vertebrates, Erythropoietin (Epo) contributes to beneficial functions in a variety of non-hematopoietic tissues including the nervous system. Epo protects cells from apoptosis, reduces inflammatory responses and supports re-establishment of compromised functions by stimulating proliferation, migration and differentiation to compensate for lost or injured cells. Similar neuroprotective and regenerative functions of Epo have been described in the nervous systems of both vertebrates and invertebrates, indicating that tissue-protective Epo-like signaling has evolved prior to its erythropoietic function in the vertebrate lineage. Epo mediates its erythropoietic function through a homodimeric Epo receptor (EpoR) that is also widely expressed in the nervous system. However, identification of neuroprotective but non-erythropoietic Epo splice variants and Epo derivatives indicated the existence of other types of Epo receptors. In this review, we summarize evidence for potential Epo receptors that might mediate Epo’s tissue-protective function in non-hematopoietic tissue, with focus on the nervous system. In particular, besides EpoR, we discuss three other potential neuroprotective Epo receptors: (1) a heteroreceptor consisting of EpoR and common beta receptor (βcR), (2) the Ephrin (Eph) B4 receptor and (3) the human orphan cytokine receptor-like factor 3 (CRLF3).

show abstract

Erythropoietin Dampens Injury-Induced Microglial Motility

Cited by 13 publications

References 19 publications

Widespread Expression of Erythropoietin Receptor in Brain and Its Induction by Injury

Widespread Expression of Erythropoietin Receptor in Brain and Its Induction by Injury

Erythropoietin Improves Atrophy, Bleeding and Cognition in the Newborn Intraventricular Hemorrhage

Alternative Erythropoietin Receptors in the Nervous System

Contact Info

Product

Resources

About