期刊
CRITICAL CARE MEDICINE
卷 39, 期 9, 页码 2099-2105出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CCM.0b013e31821cb7b2
关键词
brain edema; carbamylated erythropoietin; erythropoietin; magnetic resonance diffusion-weighted imaging; magnetic resonance imaging; neurological outcome; traumatic brain injury
资金
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- Institut pour la Recherche sur la Moelle Epiniere et l'Encephale (IRME)
- Association Francaise contre les Myopathies (AFM)
- Centre National de la Recherche Scientifique (CNRS)
- Ministere de l'Education, de la Recherche et de la Technologie, France
Objective: To investigate the effects of carbamylated erythropoietin, a modified erythropoietin lacking erythropoietic activity, on brain edema and functional recovery 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 (traumatic brain injury-saline) or carbamylated erythropoietin (50 mu g/kg; traumatic brain injury-carbamylated erythropoietin). A third group received no traumatic brain injury insult (sham-operated). Measurements and Main Results: Three series of experiments were conducted to investigate: 1) the effect of carbamylated erythropoietin on brain edema before and 1 hr after traumatic brain injury using diffusion-weighted magnetic resonance imaging and measurements of apparent diffusion coefficient (n = 10 rats per group), and the phosphorylation level of brain extracellular-regulated kinase-1/-2 was also determined to indicate the presence of an activated cell signaling pathway; 2) the time course of brain edema using magnetic resonance imaging between 4 and 6 hrs postinjury and the gravimetric technique at 6 hrs (n = 10 rats per group); and 3) motor and cognitive function over 10 days post traumatic brain injury, testing acute somato-motor reflexes, adhesive paper removal, and two-way active avoidance (n = 8 rats per group). Compared to traumatic brain injury-saline rats, rats receiving traumatic brain injury-carbamylated erythropoietin showed a significant reduction in brain edema formation at 1 hr that was sustained until 6 hrs when results were comparable with sham-operated rats. This anti-edematous effect of carbamylated erythropoietin was possibly mediated through an early inhibition of extracellular-regulated kinase-1/-2 phosphorylation. Compared to traumatic brain injury-saline rats, traumatic brain injury-carbamylated erythropoietin rats showed improved functional recovery of the acute somato-motor reflexes post traumatic brain injury, took less time to remove adhesive from the forelimbs, and showed higher percentages of correct avoidance responses. Conclusion: Our findings indicate that early posttraumatic administration of carbamylated erythropoietin reduces brain edema development until at least 6 hrs postinjury and improves neurologic recovery. Carbamylated erythropoietin can thus be considered as a potential agent in the treatment of traumatic brain injury-induced diffuse edema. (Crit Care Med 2011; 39: 2099-2105)
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