Abstract W P214: Neuroregenerative Effects of the Peptide Hormone Ghrelin After Cerebral Ischemia
Introduction: The peptide hormone Ghrelin is known as the ligand of the growth hormone secretagogue receptor and affects pituitary hormone secretion, gastrointestinal function and the cardiovascular and immune system. Recently it has been shown that Ghrelin also influences key mechanisms of the CNS. Ghrelin crosses the blood-brain barrier and binds to hippocampal neurons thereby promoting dendritic spine synapse formation and proliferation of progenitor cells. These finings led to the assumption that Ghrelin might exert neuroprotective and neuroregenerative effects in the brain.
We assessed the hypothesis that a chronic pharmacological stimulation with Ghrelin promotes mechanisms of long term post-stroke neuroregeneration thereby improving functional and structural regeneration.
Methods: In order to examine long term neuroregenerative effects, Ghrelin (40 μg/kg/d) was administered starting 24 hours after photothrombotic ischemia until the end of the experiment via osmotic pumps. Functional recovery was assessed by the adhesive tape removal test and the cylinder test performed weekly for 4 weeks. Cognitive function was analysed using the Morris water maze test. Brains were removed 4 weeks after ischemia. Post-ischemic neurogenesis was quantified in the subventricular zone (SVZ) and dentate gyrus (DG) using antibodies against Bromodeoxyuridine and Doublecortin.
Results: Treatment with Ghrelin improved motoric and cognitive recovery following photothrombotic stroke. In close apposition to the enhanced functional recovery, the pharmacological stimulation with Ghrelin significantly increased the generation of newborn hippocampal neurons in the SVZ as well as in the DG of the hippocampus.
Conclusion: In the present study, we demonstrated that chronic treatment with Ghrelin promotes the structural and functional recovery following ischemia. The recently discovered neurotrophic properties and the effects on post-stroke recovery demonstrated in this study substantiate the potential of Ghrelin as a promising agent for the neuroregenerative treatment of ischemic stroke.
Author Disclosures: K. Diederich: None. A. Schmidt: None. J. Strecker: None. W. Schäbitz: None. J. Minnerup: None.
- © 2014 by American Heart Association, Inc.