Neuroprotection by erythropoietin administration after experimental traumatic brain injury

Department of Clinical Neurosciences, Neurosurgical Clinic, University of Palermo, Italy.
Brain Research (Impact Factor: 2.83). 11/2007; 1182(1):99-105. DOI: 10.1016/j.brainres.2007.08.078
Source: PubMed

ABSTRACT A large body of evidence indicates that the hormone erythropoietin (EPO) exerts beneficial effects in the central nervous system (CNS). To date, EPO's effect has been assessed in several experimental models of brain and spinal cord injury. This study was conducted to validate whether treatment with recombinant human EPO (rHuEPO) would limit the extent of injury following experimental TBI. Experimental TBI was induced in rats by a cryogenic injury model. rHuEPO or placebo was injected intraperitoneally immediately after the injury and then every 8 h until 2 or 14 days. Forty-eight hours after injury brain water content, an indicator of brain edema, was measured with the wet-dry method and blood-brain barrier (BBB) breakdown was evaluated by assay of Evans blue extravasation. Furthermore, extent of cerebral damage was assessed. Administration of rHuEPO markedly improved recovery from motor dysfunction compared with placebo group (P<0.05). Brain edema was significantly reduced in the cortex of the EPO-treated group relative to that in the placebo-treated group (80.6+/-0.3% versus 91.8%+/-0.8% respectively, P<0.05). BBB breakdown was significantly lower in EPO-treated group than in the placebo-treated group (66.2+/-18.7 mug/g versus 181.3+/-21 mug/g, respectively, P<0.05). EPO treatment reduced injury volume significantly compared with placebo group (17.4+/-5.4 mm3 versus 37.1+/-5.3 mm3, P<0.05). EPO, administered in its recombinant form, affords significant neuroprotection in experimental TBI model and may hold promise for future clinical applications.

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Available from: Domenico Gerardo Iacopino, Aug 23, 2015
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    • "By now, numerous techniques have demonstrated the neuroprotective abilities of EPO (e.g. Grasso et al., 2007; Mammis et al., 2009; Y. Zhang et al., 2009). The close association between EPO and blood-related processes originally provoked a primary research focus around the use of EPO in vascular brain injury (e.g. "
    Brain Injury - Functional Aspects, Rehabilitation and Prevention, 03/2012; , ISBN: 978-953-51-0121-5
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    • "In addition, some studies have shown that EPO administration reduces the posttraumatic brain edema and inflammation implicated in experimental TBI. (Chen et al., 2007; Grasso et al., 2007). Therefore, treatment with EPO could provide both neuroprotective and neurorestorative effects. "
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    • "EPO administration following fimbria-fornix transection promotes survival of septal cholinergic neurons in adult rats, which suggest that EPO has trophic effects on cholinergic neurons to influence their differentiation, maintenance and regeneration (Konishi et al., 1993). It is also reported to have neuroprotective effects against cerebral ischemia in rodents (Bernaudin et al., 1999; Siren et al., 2001), experimental TBI (Brines et al., 2000; Grasso et al., 2007), and experimental SCI (Gorio et al., 2002; Boran et al., 2005; Arishima et al., 2006; Cetin et al., 2006; Fumagalli et al., 2008; Yazihan et al., 2008; Fang et al., 2009; Huang et al., 2009). In particular, EPO treatment in vitro and in vivo exerts protective, anti-apoptotic effects on spinal cord cells after injury (Arishima et al., 2006; Won et al., 2007). "
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