Table 1.
Effects of rEpo following injury to the immature CNS
| Experimental model |
Species | Method | Effect of rEpo | Reference |
|---|---|---|---|---|
| Hypoxia, HI | Rat | rEpo s.c. (0--2500 U/kg) daily at P1--P5 |
Improved neurodevelopmental outcome, prevention of dopamine neuron loss |
McPherson et al 83 |
| Excitotoxicity | Mouse | Single and repetitive injections of rEpo i.p. (5000 U/kg) at P5 0--4 h after the insult |
Small therapeutic window with protection up to 1 h, no gender differences |
Keller et al 2006 50 |
| Neonatal stroke |
Rat | rEpo i.p. (10,000 U/kg) 1 h before the insult followed by daily injections until sacrifice |
Upregulation of STAT- 5 and Bcl-2, reduction of infarct volume |
Wei et al 2006 56 |
| HI | Rat | rEpo i.p. (300 U/kg) directly after hypoxia |
Positive effect on auditory processing |
McClure et al 2006 84 |
| HI | Rat | rEpo i.p. (1000 U/kg) together with the insult |
Reversed upregulation of Bax and DP5 and downregulation of Bcl-2 |
Kumral et al 2006 46 |
| Mild hypoxia | Rat | rEpo i.p. (20,000 IE/kg) together with the beginning of hypoxia |
Significant increase of neuronal death rates |
Weber et al 2005 82 |
| HI | Rat | rEpo s.c. (2500 U/kg) at the end of hypoxia |
Protection of dopaminergic neurons, improvement of neurobehavioural outcome, no reduction of infarct volume |
Demers et al 2005 55 |
| HI | Rat | rEpo i.p. (2500 U/kg) 24 h after the insult |
Attenuation of brain injury, increase of IL- 1? , decreased infiltration of leukocytes |
Sun et al 2005 49 |
| HI | Rat | rEpo i.p. (2000 U/kg) after the insult |
Reduction of injury, improvement of neurobehavioural outcome at day 42 |
Spandou et al 2005 85 |
| Neonatal stroke |
Rat | rEpo i.p. (5000 U/kg) immediately on reperfusion |
Reduction of hemispheric volume loss, improvement of functional outcome at day 21 |
Chang et al 2005 54 |
| Neonatal stroke |
Rat | rEpo i.p. (1000 U/kg) single dose 15 min after FCI or three injections (100, 1000, or 5000 U/kg) 15 min after and repeated at 1 and 2 days after the insult |
Reduction of apoptosis, activation of Janus kinase and STAT-5, upregulation of Bcl-xL , no effect on Epo-R and on NF-κB, most effective dose 1000 U/kg for 3 days |
Sola et al 2005 44 |
| HI | Rat | rEpo i.p. (300 U/kg) 24 h before the insult and for 2 consecutive days after the insult |
Reduction of mortality, reduction of DNA fragmentation, reduction of TUNEL-positive cells, activation of heat shock protein 27 |
Sun et al 2004 47 |
| NMDA- antagonist toxicity |
Rat | rEpo i.p. (5000, 10,000, 15,000, 20,000, 30,000) IU/kg together with the insult |
Reduction of apoptosis at 5000--20,000 U/kg, restoration of BDNF, GDNF mRNA, prevention of phosphorylated levels of ERK1/2 and Akt |
Dzietko et al 2004 58 |
| HI | Rat | rEpo i.p.(10,000 U/kg), non-erythropoietic asialo- Epo (80 mg/kg) 4 h before the insult |
Reduction of infarct volume, reduction of ERK activation, upregulation of SNAP-25 |
Wang et al 2004 |
| HI | I.p. Injection of naked plasmid containing Epo cDNA 24 h before the insult |
Increase of Epo protein for 14 days, reduction of apoptosis, reduced glial activation |
Wang et al 2004 86 |
|
| HI | Rat | rEpo i.p. (1000 U/kg) together with the insult |
Increase of glutathione peroxidase and decrease of lipid peroxidation |
Kumral et al 2005 87 |
| HI | Rat | rEpo i.p. (2000 U/kg) after the insult |
Prevention of DNA fragmentation |
Spandou et al 2004 48 |
| HI | Rat | rEpo i.p. (1000 U/kg) together with the insult |
Reduction of spatial memory deficits at 22 days |
Kumral et al 2004 88 |
| HI | Rat | rEpo i.p. (1000 U/kg) together with the insult |
Inhibition of nitric oxide production |
Kumral et al 2004 60 |
| HI | Rat | rEpo i.p. (1000 U/kg) together with the insult |
Reduction of infarct volume |
Kumral et al 2003 89 |
| HI | Rat | rEpo i.c.v. (20 U) after the insult |
Reduction of infarct volume |
Aydin et al 2003 90 |
| HI | Mouse | rEpo i.p.(1,000 U/kg and 5000 U/kg) 1 h before HI |
Decreased caspase-3 and NF-?B positive neurons |
Matsushita et al 2003 45 |
BDNF, brain-derived neurotrophic factor; ERK, extracellular signal-regulated protein kinase; FCI, xxxxxxxxxxxxx; GDNF, xxxxxxxxxx; HI, hypoxia--ischemia; i.c.v., intracerebroventricular; i.p., intraperitoneally; IE, xxxxxxxxxxxxxx; NF-kB, nuclear factor-κB; P, postnatal day; rEpo, recombinant erythropoietin; s.c., subcutaneously; TUNEL, xxxxxxxxxxx; U, unit.