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Abstract
Purpose
The purpose of this study was to identify the effect of ghrelin on memory impairment in a rat model of vascular dementia induced by chronic cerebral hypoperfusion.
Methods
Randomized controlled groups and the posttest design were used. We established the representative animal model of vascular dementia caused by bilateral common carotid artery occlusion and administered 80 μg/kg ghrelin intraperitoneally for 4 weeks. First, behavioral studies were performed to evaluate spatial memory. Second, we used molecular biology techniques to determine whether ghrelin ameliorates the damage to the structure and function of the white matter and hippocampus, which are crucial to learning and memory.
Results
Ghrelin improved the spatial memory impairment in the Y-maze and Morris water maze test. In the white matter, demyelination and atrophy of the corpus callosum were significantly decreased in the ghrelin-treated group. In the hippocampus, ghrelin increased the length of hippocampal microvessels and reduced the microvessels pathology. Further, we confirmed angiogenesis enhancement through the fact that ghrelin treatment increased vascular endothelial growth factor (VEGF)-related protein levels, which are the most powerful mediators of angiogenesis in the hippocampus.
Conclusion
We found that ghrelin affected the damaged myelin sheaths and microvessels by increasing angiogenesis, which then led to neuroprotection and improved memory function. We suggest that further studies continue to accumulate evidence of the effect of ghrelin. Further, we believe that the development of therapeutic interventions that increase ghrelin may contribute to memory improvement in patients with vascular dementia.
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Figure 2.
Results of the immunohistochemistry analysis. (A) Staining by NeuN in the hippocampus. (B) Staining by RECA-1 in the hippocampus. (C) Photomicrographs of callosal thickness in the corpus callosum. (D) Staining by MBP in the corpus callosum. (E) Double immunofluorescence staining for VEGF and RECA-1 demonstrates their localization in the hippocampus. Scale bar represents 100 μm. * means p<.05 when compared to the VaD group.
Figure 3.
Result of western blot analysis. (A) Western blot analysis of VEGF, VEGFR2, and pAKT. (B) Expression level of VEGF in the hippocampus. (C) Expression level of VEGFR2 in the hippocampus. (D) Expression level of pAKT in the hippocampus. * means p<.05 when compared to the VaD group.
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