Erythropoietin prevents cognition impairment induced by transient brain ischemia in gerbils

Catania, Maria Antonietta; Marciano, Maria Concetta; Parisi, Antonio; Sturiale, Alessio; Buemi, Michele; Grasso, Giovanni; Squadrito, Francesco; Caputi, Achille P.; Calapai, Gioacchino

doi:10.1016/s0014-2999(02)01292-x

Cited by 88 publications

(49 citation statements)

References 23 publications

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“…Together with previous findings (Sakanaka et al, 1998, Calapai et al, 2000, Catania et al, 2002, Wen et al, 2002, Zhang et al, 2006, our results suggest that EPO may be useful in treating ischemic incidents in humans. Live CA1 neurons were counted and the mean number was plotted for each group.…”

Section: Discussionsupporting

confidence: 88%

“…Erythropoietin is the major hormone that stimulates and regulates the production of red blood cells; in addition to its hematopoietic role, recent studies have established EPO as a potent neuroprotective peptide against ischemic brain injury (Sakanaka et al, 1998, Calapai et al, 2000, Catania et al, 2002, Chong et al, 2002, Wen et al, 2002. EPO is also demonstrated to be able to promote the phosphorylation and activation of STAT5 through JAK2 (Damen et al, 1995, Gobert et al, 1996, Parganas et al, 1998, Siren et al, 2001, Sola et al, 2005.…”

Section: Introductionmentioning

confidence: 99%

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Signal transducers and activators of transcription 5 contributes to erythropoietin-mediated neuroprotection against hippocampal neuronal death after transient global cerebral ischemia

Zhang

Wang

Cao

et al. 2007

Neurobiology of Disease

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The signal transducers and activators of transcription (STAT) proteins are a group of transcriptional factors. Among them, STAT5 initiates a pro-survival signaling cascade. So far, little has been known about the role of STAT5 in cerebral ischemia and reperfusion. This study examines the phosphorylation status of STAT5 in hippocampal CA1 in the early stage after transient global cerebral ischemia in rats. Our data show that the phosphorylation of STAT5 was increased in hippocampal CA1 at 1 hour and 3 hours ischemia. Taking advantage of the neuroprotective effect of erythropoietin (EPO) in CA1, we further demonstrated that the administration of EPO enhanced the phosphorylation of STAT5, with SATA5a being phosphorylated earlier. The enhanced phosphorylation of STAT5 in the EPO-treated group was accompanied by the upregulation of STAT5 downstream gene products, Bcl-xL and XIAP. Consequently, ischemic CA1 neuronal damage was attenuated by the administration of EPO. Both the enhancement of STAT5 phosphorylation and the neuroprotection rendered by EPO were blocked by Tyrphostin, a selective inhibitor for Janus kinase 2, which is an upstream kinase of STAT5. These findings suggest an association between the activation of STAT5 and CA1 neuronal survival after cerebral ischemia.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Signal transducers and activators of transcription 5 contributes to erythropoietin-mediated neuroprotection against hippocampal neuronal death after transient global cerebral ischemia

Zhang

Wang

Cao

et al. 2007

Neurobiology of Disease

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“…Others subjected rats to bilateral transection of the fimbria-fornix and rHuEPO treatment allowed a better posttraumatic functional recovery (Mogensen et al, 2004). We have previously demonstrated that rHuEPO prevented cognition impairment in a gerbil transient brain ischemia model (Catania et al, 2002) and neurological dysfunction following experimental subarachnoid hemorrhage in rabbits (Grasso et al, 2002a). These studies and the present findings suggest that the neuroprotective effects exerted by rHuEPO administration in models of brain damage are associated with the maintenance of neurological functions.…”

Section: Discussionsupporting

confidence: 77%

“…Although peripherally administered recombinant human EPO (rHuEPO) has shown to penetrate the blood-brain barrier (BBB) and reduce brain injury following a variety of insults (Brines et al, 2000;Digicaylioglu and Lipton, 2001;Grasso et al, 2004), its potential neuroprotective efficacy in an in vivo model of experimental TBI has been scarcely investigated (Brines et al, 2000;Lu et al, 2005;Ozturk et al, 2005;Shein et al, 2005;Siren et al, 2006;Verdonck et al, 2007;Yatsiv et al, 2005). Evidence shows widespread efficacy of rHuEPO in injury models of spinal cord (Celik et al, 2002;Gorio et al, 2002;Grasso et al, 2006), subarachnoid hemorrhage (Buemi et al, 2002a,b;Catania et al, 2002;Grasso, 2001;Grasso et al, 2002a,b;Springborg et al, 2002), retina, and the heart damage (Calvillo et al, 2003;Junk et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Neuroprotection by erythropoietin administration after experimental traumatic brain injury

et al. 2007

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A large body of evidence indicates that the hormone erythropoietin (EPO) exerts beneficial effects in the central nervous system (CNS). To date, EPO's effect has been assessed in several experimental models of brain and spinal cord injury. This study was conducted to validate whether treatment with recombinant human EPO (rHuEPO) would limit the extent of injury following experimental TBI. Experimental TBI was induced in rats by a cryogenic injury model. rHuEPO or placebo was injected intraperitoneally immediately after the injury and then every 8 h until 2 or 14 days. Forty-eight hours after injury brain water content, an indicator of brain edema, was measured with the wet-dry method and blood-brain barrier (BBB) breakdown was evaluated by assay of Evans blue extravasation. Furthermore, extent of cerebral damage was assessed. Administration of rHuEPO markedly improved recovery from motor dysfunction compared with placebo group (P < 0.05). Brain edema was significantly reduced in the cortex of the EPO-treated group relative to that in the placebo-treated group (80.6 ± 0.3% versus 91.8% ± 0.8% respectively, P < 0.05). BBB breakdown was significantly lower in EPO-treated group than in the placebo-treated group (66.2 ± 18.7 μg/g versus 181.3 ± 21 μg/g, respectively, P < 0.05). EPO treatment reduced injury volume significantly compared with placebo group (17.4 ± 5.4 mm3 versus 37.1 ± 5.3 mm3, P < 0.05). EPO, administered in its recombinant form, affords significant neuroprotection in experimental TBI model and may hold promise for future clinical applications.

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“…1,2 Neuronal cell death in the CA1 region itself is not death-dealing but results in severe deficits of memory function. [3][4][5] Since the regeneration of neuronal cells remains critically difficult at present, protection against the neuronal loss induced by ischemic injury is vital in cerebrovascular-type dementia.…”

mentioning

confidence: 99%

Postischemic administration of Sendai virus vector carrying neurotrophic factor genes prevents delayed neuronal death in gerbils

et al. 2004

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Erythropoietin prevents cognition impairment induced by transient brain ischemia in gerbils

Cited by 88 publications

References 23 publications

Signal transducers and activators of transcription 5 contributes to erythropoietin-mediated neuroprotection against hippocampal neuronal death after transient global cerebral ischemia

Signal transducers and activators of transcription 5 contributes to erythropoietin-mediated neuroprotection against hippocampal neuronal death after transient global cerebral ischemia

Neuroprotection by erythropoietin administration after experimental traumatic brain injury

Postischemic administration of Sendai virus vector carrying neurotrophic factor genes prevents delayed neuronal death in gerbils

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