The potential mechanism of recombinant human erythropoietin treatment in vivo promoting the cognitive function recovery after traumatic brain injury in mice

Abstract

Background Inflammation after traumatic brain injury (TBI) could exacerbate secondary brain injury, resulting in neuronal apoptosis and neurological deficit. It is confirmed that recombinant human erythropoietin (rhEPO) plays an important role in neuroprotection after brain injury. This article discusses the potential mechanism of rhEPO therapy that promotes the neurological function recovery after TBI by observing the changes of neutropils and neuronal apoptosis in the brain tissue of mice after fluid percussion injury (FPI). Methods Adult male C57BL/6 mice were randomly divided into 4 groups: Sham group, TBI group, rhEPO group and normal saline (NS) group. On the first, third and seventh days after FPI, 3 mice were randomly taken from each group, the brain tissue of which was obtained. Then, immunohistochemistry was adopted to observe the expression of myeloperoxidase (MPO) positive neutrophils and Caspase-3 positive neuronal cells in the hippocampal area. During seventh to eleventh day after FPI, 10 mice of each group were subjected to Morris Water Maze Test and escaping latencies were recorded. Results Compared to Sham group, the number of MPO positive neutrophils began increasing from the first day after FPI (P = 0.000, for all) and reached the peak on the third day (P = 0.000, for all) in the TBI group, NS group and rhEPO group, but reduced on the seventh day (P = 0.000, for all); whereas Caspase-3 positive neurons increased significantly 1 d after FPI, peaking on the seventh day. However, the increase of MPO positive cells and Caspase-3 positive neurons in rhEPO group was not obvious. Compared to NS group, MPO positive neutrophils and Caspase-3 positive cells reduced significantly in rhEPO group (P = 0.000, for all) 1 to 7 d after FPI in the observed time points. In the Morris Water Maze (MWM), the latency of mice in rhEPO group reduced as compared to the NS group from the third day after FPI (P = 0.013). The differences were statistically significant as time went on (P = 0.011, 0.000). Conclusion The cognition recovery of mice after FPI can be promoted by rhEPO treatment, the potential mechanism of which is related to reducing inflammation and neuron apoptosis and promoting neural function recovery.