Neuroprotection by erythropoietin administration after experimental traumatic brain injury

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 μg/g versus 181.3 ± 21 μg/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.

Multifunctional Drugs for Head Injury

“…101 Specifically, EPO-derived peptides have been shown to ameliorate the extent of concussive brain injury, the immune damage in experimental autoimmune encephalomyelitis, and the toxicity of kainite. 102 In a cryogenic model of cortical brain injury, 103 EPO administration significantly reduced vasogenic brain edema, attenuated blood-brain barrier breakdown, reduced lesion volume, and ameliorated motor dysfunction. Similarly, following traumatically induced contusion injury, EPO administration increased the neuronal density in the CA1 and CA3 region of the hippocampus, and significantly reduced the total contusion volume when administered within 6 h of injury.…”

Therapeutic Potential of Erythropoietin and its Structural or Functional Variants in the Nervous System

“…67,76 -86 Brain edema after experimental injury can effectively be attenuated by posttreatment with EPO. 76,78,83 Mechanisms which account for the beneficial actions after traumatic injuries include inhibition of apoptosis, anti-inflammatory and anti-oxidant actions, restoration of blood-brain barrier integrity, stimulation of neurogenesis, and angiogenesis, 7,8,67,76 -84 but it is not yet clear which of the neuroprotective effects of EPO are responsible for the long-term prevention of trauma-induced brain atrophy, cognitive and neurobehavioral dysfunction. 86 Recovery of both motor function and reduction of the histopathological damage by EPO and its nonerythropoietic derivatives CEPO and asialo-EPO have been reported in various, but not all, models of spinal cord injury.…”

Cognitive Recovery and Rehabilitation After Brain Injury: Mechanisms, Challenges and Support

“…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).…”