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Updated: May 12, 2026

Advanced Diffusion Imaging in The Hippocampus of Rats with Mild Traumatic Brain Injury
Published on: August 14, 2019
Changes in brain tissue oxygenation after treatment of diffuse traumatic brain injury by erythropoietin
Pierre Bouzat1, Anne Millet, Yvonnick Boue
1INSERM, U836, Grenoble, France.
Objectives:
To investigate the effects of recombinant human erythropoietin on brain oxygenation in a model of diffuse traumatic brain injury.
Design:
Adult male Wistar rats.
Setting:
Neurosciences and physiology laboratories.
Interventions:
Thirty minutes after diffuse traumatic brain injury (impact-acceleration model), rats were intravenously administered with either a saline solution or a recombinant human erythropoietin (5000 IU/kg). A third group received no traumatic brain injury insult (sham-operated).
Measurements And Main Results:
Three series of experiments were conducted 2 hours after traumatic brain injury to investigate: 1) the effect of recombinant human erythropoietin on brain edema using diffusion-weighted magnetic resonance imaging and measurements of apparent diffusion coefficient (n = 11 rats per group); local brain oxygen saturation, mean transit time, and blood volume fraction were subsequently measured using a multiparametric magnetic resonance-based approach to estimate brain oxygenation and brain perfusion in the neocortex and caudoputamen; 2) the effect of recombinant human erythropoietin on brain tissue PO₂ in similar experiments (n = 5 rats per group); and 3) the cortical ultrastructural changes after treatment (n = 1 rat per group). Compared with the sham-operated group, traumatic brain injury saline rats showed a significant decrease in local brain oxygen saturation and in brain tissue PO₂ alongside brain edema formation and microvascular lumen collapse at H2. Treatment with recombinant human erythropoietin reversed all of these traumatic brain injury-induced changes. Brain perfusion (mean transit time and blood volume fraction) was comparable between the three groups of animals.
Conclusion:
Our findings indicate that brain hypoxia can be related to microcirculatory derangements and cell edema without evidence of brain ischemia. These changes were reversed with post-traumatic administration of recombinant human erythropoietin, thus offering new perspectives in the use of this drug in brain injury.
