Abstract
Vascular illness of the brain constitutes the third cause of death and the first cause of disability in Cuba and many other countries. Presently, no medication has been registered as a neuroprotector. Neuroprotection with intranasal Neuro-EPO (EPO, erythropoietin) has emerged as a multifunctional therapy that plays a significant role in neural survival and functional recovery in an animal model of stroke. On the other hand, there is limited access to the brain through the blood brain barrier (BBB) for intravenously applied EPO, and the high EPO dosages needed to obtain a protective effect increase the danger of elevated hematocrit levels and practically exclude chronic or subchronic treatment with EPO. A promising approach has been recently developed with a nonerythropoietic variant of EPO, Neuro-EPO, with low sialic acid content, a very short plasma half-life, and without erythropoietic activity, probably similar to endogenous brain EPO. The objective of this work was to determine the neuroprotective effect of intranasal Neuro-EPO in comparison with the human recombinant EPO injected intraperitoneally in the acute phase of cerebral ischemia, employing the common carotid artery occlusion model in gerbils. Neuro-EPO has demonstrated a better neuroprotective effect, evidenced through increased viability, improvements of the neurological state and cognitive functions, as well as protection of the CA3 region of the hippocampus, temporal cortex, and the thalamus. In conclusion, the intranasal application of Neuro-EPO has a better neuroprotective effect than intraperitoneal EPO, evidenced by the significant improvement of neurological, cognitive, and histological status in the animal model of stroke employed.
Highlights
Cerebrovascular diseases (CVD) constitute the third cause of death and the first cause of disability for adults in Cuba[1] and in many developed countries[2]
Survival percentage for the three treated groups was significantly lower than for the control group, but the survival of the group treated with Neuro-EPO IN was higher than that of animals treated with vehicle and EPO IP, comparison with the latter did not achieve statistical significance (Fig. 1)
Spontaneous Exploratory Activity Analyzing the slopes of the habituation curves in the open field test (Fig. 3), it could be established that in all the experimental groups, except the group tested with the vehicle, significant differences existed between the habituation curves before and after carotid occlusion. These differences in the control group and in the group treated with Neuro-EPO IN were positive, indicating that these animals were able to recognize the field, while in the groups treated with the vehicle and EPO IP, it was negative, indicating a lack of recognition of the previously explored field
Summary
Cerebrovascular diseases (CVD) constitute the third cause of death and the first cause of disability for adults in Cuba[1] and in many developed countries[2]. The variant of greatest incidence is ischemic CVD, with a smaller mortality than hemorrhagic CVD, but with more impact on the loss of quality of life[2]. There are two specific therapeutic strategies for the treatment of acute ischemic stroke. The first is based on restoring the blood flow and the second is based on increasing the survival of the cells of the nerve tissue (neuroprotection) after the injury to the central nervous system (CNS). There are no neuroprotectant drugs with sufficient efficacy and specificity for the treatment of acute stroke[3]. Many compounds with therapeutically promising results in animal studies have not had the same success in the clinical setting[4,5]
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