The neuroprotective effects of erythropoietin following traumatic brain injury in rats through the AMP-activated protein kinase pathway: A behavioral, biochemical, and histological study.

BACKGROUND

While some animal studies have shown that erythropoietin (EPO) can reduce neuronal death and improve cognitive outcomes after traumatic brain injury (TBI), inconsistencies exist in research findings, possibly due to differences in dosage, timing, and injury models. Specifically, the role of EPO in modulating the AMP-activated protein kinase (AMPK) pathway remain unclear. Thus, this study aims to address these gaps by investigating the effects of EPO on neurobehavioral outcomes, brain edema, blood-brain barrier (BBB) permeability, and the AMPK pathway in a severe TBI rat model.

METHODS

112 male Albino Wistar rats were traumatized by free-fall weight dropping Marmarou TBI induction method in eight groups (14 rats each): Intact, Sham, TBI, Saline (TBI + saline injection as placebo), intraperitoneal injection of EPO in 2500, 5000, and 10000 IU/kg doses, and Compound-C (TBI + Compound-C + EPO 5000) group. Cerebral edema, BBB permeability (via Evans blue method), veterinary coma scale (VCS), beam-walk (BW), beam-balance (BB), and p-AMPK/AMPK ratio (through enzyme-linked immunosorbent assay) were evaluated after trauma.

RESULTS

Administration of EPO at 2500 and 5000 IU/kg yielded lower brain water content, improved BBB integrity, better VCS, BW, and BB scores, and higher p-AMPK/AMPK ratio (all P < 0.01). Though the 5000 IU/kg dose was also effective, the 2500 IU/kg dose exhibited superior results. Notably, an escalation to 10000 IU/kg or addition of Compound-C worsened the results, suggesting a dose-dependent threshold for EPO's efficacy, and the potential role of AMPK pathway, respectively.

CONCLUSION

Our results suggest that EPO may exert neuroprotective effects in TBI-induced rats via modification of the AMPK pathway.