Abstract
Purpose: To explore the effect of recombinant human erythropoietin (r-HuEPO) on apoptosis in rats after traumatic brain injury.Methods: A total of 48 traumatic brain-injured Sprague Dawley (SD) rats were obtained by improved Feeney’s traumatic brain injury model, and were randomly divided into four groups: normal salinetreated rats (control) and rats treated with r-HuEPO at doses of 1000 U/kg, 3000 U/kg and 5000 U/kg. Brain tissues were collected on the 7th day after trauma surgery. Apoptotic cells, and NF-kappa B (NFĸB)-, c-myc-, and Fas/Fasl-positive cells were identified in brain tissues by immunohistochemical assay.Results: After treatment with r-HuEPO (3000 and 5000 U/kg), expression of NF-κB and Fas/Fasl were significantly decreased (p < 0.05) compared to control rats, especially at the 5000 U/kg dose (p < 0.01). However, for c-myc, no significant difference was observed between r-HuEPO treatment and control groups (p > 0.05). Compared to the 1000 U/kg r-HuEPO group, Fas/Fasl expression levels were significantly lower in the 3000 and 5000 U/kg r-HuEPO groups (p < 0.05). Additionally, expression of NF-κB and Fasl in the 5000 U/kg r-HuEPO group was significantly lower than that in the 3000 U/kg r- HuEPO group (p < 0.05). Moreover, the number of apoptotic cells in the r-HuEPO group (5000 U/kg) was significantly lower than in the control group (p < 0.05).Conclusion: Thus, r-HuEPO may be beneficial for treating traumatic brain injury via inhibition of NFkappa B and Fas/Fasl expressions.Keywords: Recombinant human erythropoietin, NF-kappa B, Traumatic brain injury, Apoptosis, Neuronal damage, Fas/Fasl expression
Highlights
Traumatic brain injury (TBI) is a major cause of death and persistent disability [1]
Compared with the 1000 U/kg rHuEPO treated group, the positive expressions of c-myc and Fatty acid synthase (Fas)/Fas and its ligand (Fasl) were significantly lower in 3000 U/kg recombinant human erythropoietin (r-HuEPO) group (p < 0.05), and the positive expression levels of NF-κB and Fas/Fasl in 5000 U/kg r-HuEPO treated group were significantly lower (p < 0.05)
The results indicated that the number of apoptotic cells in r-HuEPO treated group (5000 U/kg) was significantly lower compared with the control group (p < 0.05, Plate 2)
Summary
Traumatic brain injury (TBI) is a major cause of death and persistent disability [1]. The mechanisms underlying secondary brain damage following TBI are complex and involve two main stages: traumatic cerebral edema and delayed neuronal damage [1,2,3]. EPO could protect the nerves from secondary brain damage after TBI by relieving cerebrum edema [11], facilitating neuronal regeneration [12], lowering toxicity of excitatory amino acid neurotransmitters [13], and playing anti-oxidative effect [14]. Our present study used the r-HuEPO to treat traumatic brain injury in rats, and explore the effects of r-HuEPO on the expressions of NF-kB, c-myc and Fas/Fasl in brain tissue. The NF-κB-, c-myc- and Fas/Faslpositive cells, as well as apoptotic cells in brain tissues were detected by immuno-histochemistry assay.
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