• Nicole E Lopez, Gaston Lindsay, Lopez R Karina, Hageny A Mary, James Putnam, Brian Eliceiri, Raul Coimbra, and Vishal Bansal.
• Division of Trauma, Surgical Critical Care and Burns, Department of Surgery, University of California San Diego, San Diego, CA.
• J. Surg. Res. 2014 Mar 1;187(1):230-6.

BackgroundPharmacologic therapy for traumatic brain injury (TBI) has remained relatively unchanged for decades. Ghrelin, an endogenously produced peptide, has been shown to prevent apoptosis and blood-brain barrier dysfunction after TBI. We hypothesize that ghrelin treatment will prevent neuronal degeneration and improve motor coordination after TBI.Materials And MethodsA weight drop model created severe TBI in three groups of BALB/c mice: Sham, TBI, and TBI + ghrelin (20 μg intraperitoneal ghrelin). Brain tissue was examined by hematoxylin and eosin and Fluoro-Jade B (FJB) staining to evaluate histologic signs of injury, cortical volume loss, and neuronal degeneration. Additionally, motor coordination was assessed.ResultsGhrelin treatment prevented volume loss after TBI (19.4 ± 9.8 mm(3)versus 71.4 ± 31.4 mm(3); P < 0.05). Similarly, although TBI increased FJB-positive neuronal degeneration, ghrelin treatment decreased FJB staining in TBI resulting in immunohistologic patterns similar to sham. Compared with sham, TBI animals had a significant increase in foot faults at d 1, 3, and 7 (2.75 ± 0.42; 2.67 ± 0.94; 3.33 ± 0.69 versus 0.0 ± 0.0; 0.17 ± 0.19; 0.0 ± 0.0; P < 0.001). TBI + ghrelin animals had significantly decreased foot faults compared with TBI at d 1, 3, and 7 (0.42 ± 0.63; 0.5 ± 0.43; 1.33 ± 0.58; P versus TBI <0.001; P versus sham = NS).ConclusionsGhrelin treatment prevented post-TBI cortical volume loss and neurodegeneration. Furthermore, ghrelin improved post-TBI motor deficits. The mechanisms of these effects are unclear; however, a combination of the anti-apoptotic and inflammatory modulatory effects of ghrelin may play a role. Further studies delineating the mechanism of these observed effects are warranted.Copyright © 2014 Elsevier Inc. All rights reserved.

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