Ghrelin Reduces Infiltrating Inflammatory Cells

Abstract

Traumatic brain injury (TBI) is one of the leading causes of injury related death and disability in the United States. Although cell loss during primary injury is immediate, therapeutic interventions are possible to reduce secondary injury. This wave of injury includes the inflammatory response, which is mediated by the activation of resident microglia, infiltration of leukocytes and release of proinflammatory cytokines at the site of injury. The hormone Ghrelin has been demonstrated to be beneficial in the pathology of TBI, so we hypothesize that Ghrelin may influence the infiltrating inflammatory cell profile, including microglia, monocytes/neutrophils, and lymphocytes. In the present study, C57Bl/6 mice were divided into sham, TBI and TBI/Ghrelin treatment groups and subjected to a weight drop model of severe TBI. Brain tissue was analyzed one week post-TBI to evaluate Ghrelin’s impact on infiltrating leukocytes and resident microglia. Histology techniques were utilized in assessing the overall physiology and pathology of the TBI and flow cytometric analysis of cells was used to identify and quantify cell populations. Ghrelin treatment reduced cortical cavity volume as well as significantly reduced total infiltrating inflammatory leukocytes after TBI. Ghrelin did not significantly affect the leukocyte subpopulations, which suggests that Ghrelin may cause acute changes in the immune system that lead to prolonged neuroprotection. Ghrelin administration did not significantly alter the activation state of the microglia, reinforcing that Ghrelin regulation of inflammatory cells may occur through vascular permeability and anti-inflammation. The underlying biology behind Ghrelin’s neuroprotection needs further research; however, the observed reduction of infiltrating inflammatory cells underscores the clinical implications of Ghrelin as a suitable therapy for TBI.