Erythropoietin and the nervous system

Genç, Şermin; Köroğlu, Tolga; Genç, Kürşad

doi:10.1016/j.brainres.2003.12.037

Cited by 164 publications

(115 citation statements)

References 102 publications

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“…Accordingly, we observed a reduction of cell survival with prolonged hypoxic exposure and significantly reduced expression of two important target genes, namely Epo and Glut-1, after treatment with roscovitine confirming impairment of the hypoxic signaling cascade. Other in vitro models have also shown that neurons exposed to hypoxia significantly upregulate Glut-1 and Epo (Genc et al, 2004) mRNA and protein levels.…”

Section: Discussionmentioning

confidence: 94%

Cdk5 interacts with Hif-1α in neurons: A new hypoxic signalling mechanism?

2011

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Section: Discussionmentioning

confidence: 94%

Cdk5 interacts with Hif-1α in neurons: A new hypoxic signalling mechanism?

2011

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“…This antagonizing effect was associated with perturbation of the oscillatory calcium signal triggered by mGluR5 activation. EPO exerts its biological functions through a cell surface receptor, which has been known to be expressed in the cerebral cortex, midbrain, and hippocampus of the CNS (1,3,26). EPO is expressed both in neurons and astrocytes and recent studies demonstrated that EPO receptor (EPOR) is expressed in cultured astrocytes (27).…”

Section: Epo Inhibits Group I Mglur-induced Increase In Hypotonic Swementioning

confidence: 99%

“…recent years emerged as one of the most efficient neuroprotective agents (1)(2)(3). It is well documented from both experimental and clinical studies that erythropoietin (EPO) attenuates the degree of brain damage after stroke (4)(5)(6).…”

mentioning

confidence: 99%

Erythropoietin modulation of astrocyte water permeability as a component of neuroprotection

Gunnarson

Song

Kowalewski

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Disturbed brain water homeostasis with swelling of astroglial cells is a common complication in stroke, trauma, and meningitis and is considered to be a major cause of permanent brain damage. Astroglial cells possess the water channel aquaporin 4 (AQP4). Recent studies from our laboratory have shown that glutamate, acting on group I metabotropic glutamate receptors (mGluRs), increases the permeability of astrocyte AQP4, which, in situations of hypoxia-ischemia, will increase astrocyte water uptake. Here we report that erythropoietin (EPO), which in recent years has emerged as a potent neuro-protective agent, antagonizes the effect of a group I mGluR agonist on astrocyte water permeability. Activation of group I mGluRs triggers fast and highly regular intracellular calcium oscillations and we show that EPO interferes with this signaling event by altering the frequency of the oscillations. These effects of EPO are immediate, in contrast to the neuroprotective effects of EPO that are known to depend upon gene activation. Our findings indicate that EPO may directly reduce the risk of astrocyte swelling in stroke and other brain insults. In support of this conclusion we found that EPO reduced the neurological symptoms in a mouse model of primary brain edema known to depend upon AQP4 water transport.aquaporin 4 ͉ brain edema ͉ glutamate E rythropoietin, the major haemopoietic growth factor, has in recent years emerged as one of the most efficient neuroprotective agents (1-3). It is well documented from both experimental and clinical studies that erythropoietin (EPO) attenuates the degree of brain damage after stroke (4-6). Stroke is associated with a massive release of glutamate and experimental studies have indicated that EPO also protects from glutamatetriggered neurotoxicity (7). EPO acts by preventing the destruction of viable tissue surrounding the site of an injury, that is, the penumbra that develops during the first 24-48 h after a brain insult (1). Cell swelling is one of the characteristic features of the penumbra (8, 9).Mounting evidence suggests that water uptake in astrocytes via the water channel aquaporin 4 (AQP4) is an important factor contributing to post-ischemic cell swelling (10, 11). Immunohistochemical studies have indicated a colocalization between EPO receptors and AQP4 in the brain (12, 13), particularly in glial cells at the interface between the brain parenchyma and the periphery. This raises the question whether EPO may modulate astrocyte water permeability and whether this effect may attenuate astrocyte water uptake after a brain insult. We have in a recent study demonstrated that glutamate increases astrocyte water permeability via activation of AQP4 (14). In the present study we have tested the possibility that EPO may counteract the effect of glutamate on astrocyte water permeability.To document the tissue protective role of EPO in brain edema, we first tested whether EPO reduces symptoms in a mouse model of water intoxication known to depend upon glial AQP4 (11). Observing a robust eff...

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“…It is predominantly produced in the fetal liver and adult kidney, but can also be expressed by neurons, glial cells and the cerebrovascular endothelium. It was shown that EPO could actin an angiogenic, neuroprotective and neurotrophic manner in addition to its promoting role in haematopoiesis [34] . The efficacy of EPO was evaluated in patients with optic neuritis due to its neuroprotective properties by Sühs and colleagues [35] .…”

Section: Erythropoietinmentioning

confidence: 99%