Ghrelin decreases motor deficits after traumatic brain injury

Background: Pharmacologic 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 methods: A weight drop model created severe TBI in three groups of BALB/c mice: Sham, TBI, and TBI þ ghrelin (20 mg 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. Results: Ghrelin 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 FJBepositive 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 þ 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 ¼ NS). Conclusions: Ghrelin 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.