Neuropathological Changes After Induced Traumatic Brain Injury and Administration of Erythropoietin

Abstract

Introduction Head trauma produces a dynamic process characterized by a cascade of metabolic, cellular and molecular events. Erythropoietin (EPO) has been shown to have neuroprotective effects in models of traumatic brain injury (TBI). However the exact acute mechanism of in vivo action remains unclear. This study was performed to compare acute pathological changes following TBI with and without systemically administered EPO. Methods TBI percussion hub was inserted into right parietal lobe of 10 Sprague-Dawley rats. Rats were allowed to recover for 5 days. TBI of 2.5–2.8 atm was induced via fluid percussion device. Rats received 5000 Units/Kilogram EPO (ip) or saline (ip) 30 min post-TBI. Rats were sacrificed 10 hours after TBI. Brains were stained with H&E, tyrosine hydroxylase, EPO-receptor and cleaved caspase. Results Rats receiving EPO 30 min post-TBI showed significant decrease in edema and neuronal cell death as measured by H&E staining (p<0.01), and increased tyrosine hydroxylase expression in the substantia nigra and striatum (p<0.01). Further rats receiving EPO showed increased cortical rim EPO-receptor expression and decreased amount of cells positive for cleaved caspase (p<0.01) as compared with saline controls. Conclusions EPO given 30 min post-TBI shows decreased amount of necrosis and edema, decreased early apotosis, increased EPO-receptors, and increased expression of dopaminergic neurons. This data elucidates acute in vivo effects of EPO in brain microenvironment following TBI. Our results suggest that EPO's neuroprotective effect and mechanism may be a result of decreasing necrosis, slowing early apoptosis, upregulating EPO receptors and inducing the dopaminergic pathway.