Post-ischemic continuous infusion of erythropoeitin enhances recovery of lost memory function after global cerebral ischemia in the rat

Abstract

BackgroundErythropoietin (EPO) and its covalently modified analogs are neuroprotective in various models of brain damage and disease. We investigated the effect on brain damage and memory performance, of a continuous 3-day intravenous infusion of EPO, starting 20 min after a transient 10 minute period of global cerebral ischemia in the rat.ResultsWe found no effect on selective neuronal damage in the CA1 region of the hippocampus, neocortical damage and damage to the striatum assessed at 7 days after ischemia. Also, no differences were observed in sensori-motor scores between EPO treated and saline treated ischemic animals. In contrast, memory performance was significantly improved in the EPO treated group. Saline treated injured animals (n = 7) failed in a test assessing recovery of spatial memory (6/6 and 5/6), while EPO treated animals had few and none failures (0/7 and 1/7).ConclusionWe conclude that although post-ischemic treatment with EPO is not neuroprotective in a model of cardiac arrest brain ischemia, its markedly positive effect on brain plasticity and recovery of memory function warrants consideration as treatment of cardiac arrest patients.

DNA methylation is necessary for erythropoietin to improve spatial learning and memory in SAMP8 mice

“…This fact reflected that motor performances of mice in different groups were similar. Therefore the behavior changes in this study reveal that EPO is capable of promoting spatial learning and memory instead of motor abilities, which is consistent with earlier studies (Undén et al, 2013;Adamcio et al, 2008;Hamidi et al, 2013).…”

“…Erythropoietin (Epo) is a 34-kDa glycoprotein hormone that was originally considered an erythropoietic cytokine and approved by the Food and Drug Administration for the treatment of anemia, but has also been shown to reduce cognitive loss due to mechanical injury to the hippocampus (Zhang et al, 2012) or protect sensitive hippocampal neurons from both focal (Hralová et al, 2014) and global (Undén et al, 2013) ischemic brain injury. EPO improves long-term potentiation and memory not only in young healthy mice (Adamcio et al, 2008) but also in different models of dementia (Hamidi et al, 2013;Kumar et al, 2010).…”

Erythropoietin Promotes Neural Plasticity and Spatial Memory Recovery in Fimbria-Fornix-Lesioned Rats

“…44,45 As mentioned earlier, neuroprotective effects of EPO have been reported in different animal models. [1][2][3][4][5][8][9][10][11] The lack of presumptive neuroprotective effects of EPO based on behavioral recovery in our results was surprising, particularly considering previous reports showing that EPO injected shortly after FF lesions improved behavioral performance in the water maze. 46 However, a preliminary explanation could emerge from the simple fact that our FF-lesioned animals showed no sign of training-induced recovery, while this is clearly the case in the Mogensen's study.…”

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“…9,[11][12][13][28][29][30][31]41,50,53 Neurological recovery can be further assessed with quantitative behavioral tests in rodents, such as the T maze or the Morris maze test. [59][60][61] In addition to the clinical evaluation of neurological function, histopathological damages are also usually evaluated in most experimental studies.…”