Neuroprotective effects of erythropoietin on brain edema, blood brain barrier permeability and neurological points after severe traumatic brain injury in male rats: role of AMPK

Background and Aim : Erythropoietin (Epo) is a cytokine that exists in all vertebrate groups. The main function of Epo in the nervous system is protection against apoptosis, reducing inflammatory responses and helping to migrate, and differentiating cells to replace dead or damaged cells. Therefore, in this study, we investigated the effects of neuroprotective erythropoietin after induction of brain inflammation in rats.Methods : The male Albino wistar rats received different doses of . Clarithromycin (2500, 5000, 10000 mg/kg, i.p.).All animals were intubated before surgery. In the TBI groups, diffuse TBI was induced by Marmarou method using a TBI induction device. The severe TBI was induced using a weight 450 gr.In the sham groups, all stages of induction of TBI were performed except dropping weight on the head. The disruption of Blood brain- barrier (BBB) was evaluated 6 h post- TBI. The neurologic score( VCS ) and brain water content, the beam-walk –balance task (WB) were determined before trauma, on trauma time(D0), and 1 day(D1) and 2 DAy (D2) and 3 Day (D3) After TBI anaesthetized animals were sacrificed and the brain was removed and then analaysis mmp with Elisa assay.Results : Our results showed that traumatic brain injury led to significant brain edema and disrupt of blood brain- barrier and neurological defect and vestibulomotor dysfunction in the rat brain and decrease mmp in serume. Erythropoietin (2500,5000mg/ kg) could attenuated brain edema, improved BBB and vestibulomotor dysfunction in compare with TBI control group (P<0.001) but in 50 dose results were better.Conclusion : These findings showed that Erythropoietin has a prominent role in TBI outcome’s and perhaps protect neurons through modulating inflammatory and antioxidant pathways.

Keywords:

Erythropoietin , TBI , neuroprotective , mmp , rat