Erythropoietin improves long-term spatial memory deficits and brain injury following neonatal hypoxia–ischemia in rats

Kumral, Abdullah; Uysal, Nazan; Tugyan, Kazim; Sönmez, Ataç; Yılmaz, Osman; Gökmen, Necati; Kıray, Müge; Genç, Şermin; Duman, Nuray; Köroğlu, Tolga; Özkan, Hasan

doi:10.1016/j.bbr.2003.11.002

Cited by 172 publications

(98 citation statements)

References 49 publications

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“…Neurobehavioral improvement after EPO administration has been reported in other studies where different models of brain injury were used. In this regard, it has been demonstrated that rat pups given rHuEPO had a significantly better performance in the Morris water maze test compared with untreated animals (Kumral et al, 2004). Others subjected rats to bilateral transection of the fimbria-fornix and rHuEPO treatment allowed a better posttraumatic functional recovery (Mogensen et al, 2004).…”

Section: Discussionmentioning

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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Section: Discussionmentioning

confidence: 99%

Neuroprotection by erythropoietin administration after experimental traumatic brain injury

et al. 2007

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“…6,33,44,[55][56][57][58][59][60][61][62][63][64] Earlier studies used the direct intracerebroventricular route of administration of EPO to demonstrate its potent tissue protective activity in focal and global models of cerebral ischemia. [2][3][4] EPO, as a large, highly glycosylated negatively charged molecule, was not expected to penetrate the blood-brain barrier.…”

Section: Stroke and Cerebral Ischemiamentioning

confidence: 99%

“…Intriguingly, EPO and its derivatives reduce histological damage and improve functional outcome when given as intraperitoneal or even intranasal post-treatment after experimental stroke and hypoxia-ischemia. 33,44,[55][56][57][58][59][60][61][62][63][64]73 A typical example of the functional improvement by EPO in sensorimotor deficits after a focal stroke is presented in Figure 2 (Sirén and Ehrenreich, unpublished own preclinical data in preparation of the "Göttingen EPO Stroke Study," see as follows).…”

Section: Stroke and Cerebral Ischemiamentioning

confidence: 99%

Therapeutic Potential of Erythropoietin and its Structural or Functional Variants in the Nervous System

et al. 2009

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Summary:The growth factor erythropoietin (EPO) and erythropoietin receptors (EPOR) are expressed in the nervous system. Neuronal expression of EPO and EPOR peaks during brain development and is upregulated in the adult brain after injury. Peripherally administered EPO, and at least some of its variants, cross the blood-brain barrier, stimulate neurogenesis, neuronal differentiation, and activate brain neurotrophic, antiapoptotic, anti-oxidant and anti-inflammatory signaling. These mechanisms underlie their tissue protective effects in nervous system disorders. As the tissue protective functions of EPO can be separated from its stimulatory action on hematopoiesis, novel EPO derivatives and mimetics, such as asialo-EPO and carbamoylated EPO have been developed. While the therapeutic potential of the novel EPO derivatives continues to be characterized in preclinical studies, the experimental findings in support for the use of recombinant human (rh)EPO in human brain disease have already been translated to clinical studies in acute ischemic stroke, chronic schizophrenia, and chronic progressive multiple sclerosis. In this review article, we assess the studies on EPO and, in particular, on its structural or functional variants in experimental models of nervous system disorders, and we provide a short overview of the completed and ongoing clinical studies testing EPO as neuroprotective/neuroregenerative treatment option in neuropsychiatric disease.

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“…Recently, a number of medicinal plants have been shown to protect neurons against ischemic stroke [10]. Matricaria chamomilla is native to the Mediterranean region but is now widely disturbed worldwide.…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effect of Matricaria chamomilla Extract on Motor Dysfunction Induced by Transient Global Cerebral Ischemia and Reperfusion in Rat

Moshfegh

Setorki

2017

Zahedan J Res Med Sci

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Erythropoietin improves long-term spatial memory deficits and brain injury following neonatal hypoxia–ischemia in rats

Cited by 172 publications

References 49 publications

Neuroprotection by erythropoietin administration after experimental traumatic brain injury

Neuroprotection by erythropoietin administration after experimental traumatic brain injury

Therapeutic Potential of Erythropoietin and its Structural or Functional Variants in the Nervous System

Neuroprotective Effect of Matricaria chamomilla Extract on Motor Dysfunction Induced by Transient Global Cerebral Ischemia and Reperfusion in Rat

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