The relationship between erythropoietin pretreatment with blood–brain barrier and lipid peroxidation after ischemia/reperfusion in rats

Bahçekapılı, Nesrin; Üzüm, Gülay; Gökkuşu, Cahide; Kuru, Alev; Ziylan, Y. Ziya

doi:10.1016/j.lfs.2006.12.014

Cited by 34 publications

(22 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…23,26 The reperfusion phase leads to generation of reactive oxygen radicals and lipid peroxidation that are highly noxious to the brain's capillary endothelial cells and its complex tight junctions, which are mostly responsible for the integrity of the BBB. 2,4 Erythropoietin has been shown to increase nitric oxide synthesis in endothelial cells and, under oxidative stress conditions, nitric oxide may scavenge reactive oxygen species. 3,39 This detoxification also prevents membrane lipid peroxidation and consequential additional disruption of the BBB in I/R.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of erythropoietin pretreatment in a rodent model of transient middle cerebral artery occlusion

Ratilal

Arroja

Rocha

et al. 2014

JNS

View full text Add to dashboard Cite

Object There is an unmet clinical need to develop neuroprotective agents for neurosurgical and endovascular procedures that require transient cerebral artery occlusion. The aim in this study was to explore the effects of a single dose of recombinant human erythropoietin (rhEPO) before middle cerebral artery (MCA) occlusion in a focal cerebral ischemia/reperfusion model. Methods Twenty-eight adult male Wistar rats were subjected to right MCA occlusion via the intraluminal thread technique for 60 minutes under continuous cortical perfusion monitoring by laser Doppler flowmetry. Rats were divided into 2 groups: control and treatment. In the treated group, rhEPO (1000 IU/kg intravenously) was administered 10 minutes before the onset of the MCA ischemia. At 24-hour reperfusion, animals were examined for neurological deficits, blood samples were collected, and animals were killed. The following parameters were evaluated: brain infarct volume, ipsilateral hemispheric edema, neuron-specific enolase plasma levels, parenchyma histological features (H & E staining), Fluoro-Jade–positive neurons, p-Akt and total Akt expression by Western blot analysis, and p-Akt–positive nuclei by immunohistochemical investigation. Results Infarct volume and Fluoro-Jade staining of degenerating neurons in the infarct area did not vary between groups. The severity of neurological deficit (p < 0.001), amount of brain edema (78% reduction in treatment group, p < 0.001), and neuron-specific enolase plasma levels (p < 0.001) were reduced in the treatment group. Perivascular edema was histologically less marked in the treatment group. No variations in the expression or localization of p-Akt were seen. Conclusions Administration of rhEPO before the onset of 60-minute transient MCA ischemia protected the brain from this insult. It is unlikely that rhEPO pretreatment leads to direct neuronal antiapoptotic effects, as supported by the lack of Akt activation, and its benefits are most probably related to an indirect effect on brain edema as a consequence of blood-brain barrier preservation. Although research on EPO derivatives is increasing, rhEPO acts through distinct neuroprotective pathways and its clinical safety profile is well known. Clinically available rhEPO is a potential therapy for prevention of neuronal injury induced by transitory artery occlusion during neurovascular procedures.

show abstract

Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of erythropoietin pretreatment in a rodent model of transient middle cerebral artery occlusion

Ratilal

Arroja

Rocha

et al. 2014

JNS

View full text Add to dashboard Cite

show abstract

“…The increase in BBB permeability during pentylentetrazol induced seizures is prevented by rhEPO [25]. Also, it prevents BBB disruption induced by global ischemia in rats [26]. One proposed mechanism of this protection is through the inhibition of NO formation [20].…”

Section: Discussionmentioning

confidence: 99%

Erythropoietin Prevents Blood Brain Barrier Damage Induced by Focal Cerebral Ischemia in Mice

Liu

Ogle

et al. 2007

Neurochem Res

View full text Add to dashboard Cite

Recombinant human erythropoietin (rhEPO), a neurovascular protective agent, therapeutically supports angiogenesis after stroke by enhancing endogenous up-regulation of vascular endothelial growth factor (VEGF). Increased VEGF expression has been characterized to negatively impact the integrity of the blood brain barrier (BBB), causing brain edema and secondary injury. The present study investigated the rhEPO-induced BBB protection after stroke and how it might be achieved by affecting VEGF pathway. rhEPO treatment (5,000 U/kg, i.p., 30 min before stroke and once a day for three days after stroke) reduced Evans blue leakage and brain edema after ischemia. The expression of the BBB integrity markers, occludin, alpha-catenin and beta-catenin, in the brain was preserved in animals received rhEPO. rhEPO up-regulated VEGF expression; however, the expression of VEGF receptor-2 (fetal liver kinase receptor, Flk-1) was significantly reduced in rhEPO-treated animals three days after stroke. We propose that, disregarding increased VEGF levels, rhEPO protects against ischemia-induced BBB damage at least partly by down-regulating Flk-1 expression and the response to VEGF signaling in the acute phase after stroke.

show abstract

“…Excitotoxicity induced by H-I may be enhanced by bacteria-released lipopolysaccharide in cases of intrauterine infection [12] and oxidative injury due to production of free radicals [13,14] . However, the exact mechanism underlying the PVL pathogenesis has not yet been clarified.…”

Section: Introductionmentioning

confidence: 99%

Pretreatment with Low Doses of Erythropoietin Ameliorates Brain Damage in Periventricular Leukomalacia by Targeting Late Oligodendrocyte Progenitors: A Rat Model

Mizuno¹,

Hida

Masuda

et al. 2008

Neonatology

View full text Add to dashboard Cite

Background: One of the pathological hallmarks of periventricular leukomalacia (PVL) is the selective vulnerability of late oligodendrocyte progenitors (preoligodendrocytes; preOLs) to hypoxia-ischemia (H-I). It is unknown whether recombinant human erythropoietin (rhEPO) protects preOLs in vivo. Objectives: To develop a rat PVL model in which preOLs are selectively damaged and exhibit similar pathological changes to diffuse-type human PVL, various conditions of H-I were compared in P2–P7 rats (P2 = postnatal day 2). To evaluate the effect of rhEPO on oligoprotection (preOLs), rhEPO was administered to P3 PVL rats. Methods: After counts of NG2-positive and O4-positive cells were performed in P2–P7 rats, right common carotid artery occlusion followed by 6% O₂ for 0–120 min was performed in P2–P4 rats. The mortality and histological alterations after hematoxylin/eosin staining and ED1 immunostaining were assessed 2 days after H-I. Various doses of rhEPO (1–30,000 U/kg i.p.) were administered to PVL rats 15 min before administration of 6% O₂. Results: Double-positive cells for NG2 and O4 were detected from P2, and their number gradually increased until P7. Although right common carotid artery occlusion with 6% O₂ for 60 min resulted in a relatively high proportion of deaths in P2–P4 rats, typical histological changes in the PVL diffuse component were found in most surviving P3 animals. With 50–100 U/kg rhEPO, the histological damage was attenuated. Conclusions: Histological changes similar to those seen in the PVL diffuse component were induced by H-I in P3 rats, in which preOLs were gradually developing, and a low dose of rhEPO was effective in the treatment of brain damage induced by H-I.

show abstract

The relationship between erythropoietin pretreatment with blood–brain barrier and lipid peroxidation after ischemia/reperfusion in rats

Cited by 34 publications

References 38 publications

Neuroprotective effects of erythropoietin pretreatment in a rodent model of transient middle cerebral artery occlusion

Neuroprotective effects of erythropoietin pretreatment in a rodent model of transient middle cerebral artery occlusion

Erythropoietin Prevents Blood Brain Barrier Damage Induced by Focal Cerebral Ischemia in Mice

Pretreatment with Low Doses of Erythropoietin Ameliorates Brain Damage in Periventricular Leukomalacia by Targeting Late Oligodendrocyte Progenitors: A Rat Model

Contact Info

Product

Resources

About