The efficacy of erythropoietin in treating experimental traumatic brain injury: a systematic review of controlled trials in animal models

Peng, Weijun; Xing, Zhihua; Yang, Jingjing; Wang, Yan; Wang, Weihao; Huang, Wei

doi:10.3171/2014.6.jns132577

Cited by 51 publications

(45 citation statements)

References 54 publications

(100 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In agreement with TBI studies, we detected less cell death, optic nerve degeneration, glial reactivity, and oxidative stress by systemic injection of EPO (for review see 39 ). Further, as in other models, we also detected efficacy with EPO when treatment was delayed until 24h post-injury.…”

Section: Discussionsupporting

confidence: 89%

Erythropoietin either Prevents or Exacerbates Retinal Damage from Eye Trauma Depending on Treatment Timing

Bricker-Anthony

D'Surney

Lunn³

et al. 2017

Optom Vis Sci

View full text Add to dashboard Cite

Purpose Erythropoietin (EPO) is a promising neuroprotective agent and is currently in Phase III clinical trials for the treatment of traumatic brain injury. The goal of this study was to determine if EPO is also protective in traumatic eye injury. Methods The left eyes of anesthetized DBA/2J or Balb/c mice were exposed to a single 26psi over-pressure air-wave while the rest of the body was shielded. DBA/2J mice were given intraperitoneal injections of EPO or buffer and analyses were performed at 3 or 7 days post-blast. Balb/c mice were given intramuscular injections of rAAV.EpoR76E or rAAV.eGFP either pre-or post-blast and analyses were performed at 1-month post-blast. Results EPO had a bi-modal effect on cell death, glial reactivity, and oxidative stress. All measures were increased at 3 days post-blast and decreased at 7-days post-blast. Increased retinal ferritin and NADPH oxygenases were detected in retinas from EPO-treated mice. The gene therapy approach protected against axon degeneration, cell death and oxidative stress when given after blast, but not before. Conclusions Systemic, exogenous, EPO and EPO-R76E protects the retina after trauma even when initiation of treatment is delayed by up to 3 weeks. Systemic treatment with EPO or EPO-R76E beginning before or soon after trauma may exacerbate protective effects of EPO within the retina as a result of increased iron levels from erythropoiesis and thus, increased oxidative stress within the retina. This is likely overcome with time as a result of an increase in levels of antioxidant enzymes. Either intraocular delivery of EPO or treatment with non-erythropoietic forms of EPO may be more efficacious.

show abstract

Section: Discussionsupporting

confidence: 89%

Erythropoietin either Prevents or Exacerbates Retinal Damage from Eye Trauma Depending on Treatment Timing

Bricker-Anthony

D'Surney

Lunn³

et al. 2017

Optom Vis Sci

View full text Add to dashboard Cite

show abstract

“…Erythropoietin has multiple mechanisms of action that can be beneficial for treating TBI, 14,69,90 including enhancing the survival and maturation of oligodendrocytes and neurons after injury. 38,53,97 Similar to the effect on erythroblasts in the bone marrow, unbound EPO receptors (EPORs) promote neural cell apoptosis.…”

mentioning

confidence: 99%

Imaging and serum biomarkers reflecting the functional efficacy of extended erythropoietin treatment in rats following infantile traumatic brain injury

Robinson

Winer

Berkner

et al. 2016

PED

View full text Add to dashboard Cite

OBJECTIVE Traumatic brain injury (TBI) is a leading cause of death and severe morbidity for otherwise healthy full-term infants around the world. Currently, the primary treatment for infant TBI is supportive, as no targeted therapies exist to actively promote recovery. The developing infant brain, in particular, has a unique response to injury and the potential for repair, both of which vary with maturation. Targeted interventions and objective measures of therapeutic efficacy are needed in this special population. The authors hypothesized that MRI and serum biomarkers can be used to quantify outcomes following infantile TBI in a preclinical rat model and that the potential efficacy of the neuro-reparative agent erythropoietin (EPO) in promoting recovery can be tested using these biomarkers as surrogates for functional outcomes. METHODS With institutional approval, a controlled cortical impact (CCI) was delivered to postnatal Day (P)12 rats of both sexes (76 rats). On postinjury Day (PID)1, the 49 CCI rats designated for chronic studies were randomized to EPO (3000 U/kg/dose, CCI-EPO, 24 rats) or vehicle (CCI-veh, 25 rats) administered intraperitoneally on PID1–4, 6, and 8. Acute injury (PID3) was evaluated with an immunoassay of injured cortex and serum, and chronic injury (PID13–28) was evaluated with digitized gait analyses, MRI, and serum immunoassay. The CCI-veh and CCI-EPO rats were compared with shams (49 rats) primarily using 2-way ANOVA with Bonferroni post hoc correction. RESULTS Following CCI, there was 4.8% mortality and 55% of injured rats exhibited convulsions. Of the injured rats designated for chronic analyses, 8.1% developed leptomeningeal cyst–like lesions verified with MRI and were excluded from further study. On PID3, Western blot showed that EPO receptor expression was increased in the injured cortex (p = 0.008). These Western blots also showed elevated ipsilateral cortex calpain degradation products for αII-spectrin (αII-SDPs; p < 0.001), potassium chloride cotransporter 2 (KCC2-DPs; p = 0.037), and glial fibrillary acidic protein (GFAP-DPs; p = 0.002), as well as serum GFAP (serum GFAP-DPs; p = 0.001). In injured rats multiplex electrochemiluminescence analyses on PID3 revealed elevated serum tumor necrosis factor alpha (TNFα p = 0.01) and chemokine (CXC) ligand 1 (CXCL1). Chronically, that is, in PID13–16 CCI-veh rats, as compared with sham rats, gait deficits were demonstrated (p = 0.033) but then were reversed (p = 0.022) with EPO treatment. Diffusion tensor MRI of the ipsilateral and contralateral cortex and white matter in PID16–23 CCI-veh rats showed widespread injury and significant abnormalities of functional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD); MD, AD, and RD improved after EPO treatment. Chronically, P13–P28 CCI-veh rats also had elevated serum CXCL1 levels, which normalized in CCI-EPO rats. CONCLUSIONS Efficient translation of emerging neuro-reparative interventions dictates the use of age-appropriate preclinical models with human clinical trial–compatible biomarkers. In the present study, the authors showed that CCI produced chronic gait deficits in P12 rats that resolved with EPO treatment and that chronic imaging and serum biomarkers correlated with this improvement.

show abstract

“…Administering EPO and maintaining hemoglobin >10 g/dL in patients with TBI did not result in neurobehavioral improvement, but neurological improvement occurred after 6 months41). Peng et al reported that EPO helped to treat experimental TBI by reducing lesion volume and improving neurological outcome39).…”

Section: Discussionmentioning

confidence: 99%

Effects of Quercetin and Mannitol on Erythropoietin Levels in Rats Following Acute Severe Traumatic Brain Injury

Kalemcı

Aydın

Kızmazoğlu

et al. 2017

J Korean Neurosurg Soc

View full text Add to dashboard Cite

ObjectiveThe aim of this study to investigate the normal values of erythropoietin (EPO) and neuroprotective effects of quercetin and mannitol on EPO and hematocrit levels after acute severe traumatic brain injury (TBI) in rat model.MethodsA weight-drop impact acceleration model of TBI was used on 40 male Wistar rats. The animals were divided into sham (group I), TBI (group II), TBI+quercetin (50 mg/kg intravenously) (group III), and TBI+mannitol (1 mg/kg intravenously) (group IV) groups. The malondialdehyde, glutathione peroxidase, catalase, EPO, and hematocrit levels were measured 1 and 4 hour after injury. Two-way repeated measures analysis of variance and Tukey’s test were used for statistical analysis.ResultsThe malondialdehyde levels decreased significantly after administration of quercetin and mannitol compared with those in group II. Catalase and glutathione peroxidase levels increased significantly in groups III and IV. Serum EPO levels decreased significantly after mannitol but not after quercetin administration. Serum hematocrit levels did not change significantly after quercetin and mannitol administration 1 hour after trauma. However, mannitol administration decreased serum hematocrit levels significantly after 4 hour.ConclusionThis study suggests that quercetin may be a good alternative treatment for TBI, as it did not decrease the EPO levels.

show abstract

The efficacy of erythropoietin in treating experimental traumatic brain injury: a systematic review of controlled trials in animal models

Cited by 51 publications

References 54 publications

Erythropoietin either Prevents or Exacerbates Retinal Damage from Eye Trauma Depending on Treatment Timing

Erythropoietin either Prevents or Exacerbates Retinal Damage from Eye Trauma Depending on Treatment Timing

Imaging and serum biomarkers reflecting the functional efficacy of extended erythropoietin treatment in rats following infantile traumatic brain injury

Effects of Quercetin and Mannitol on Erythropoietin Levels in Rats Following Acute Severe Traumatic Brain Injury

Contact Info

Product

Resources

About