Cerebral ischemia is a prevalent disorder affecting a large human population. While cerebral ischemia causes neuronal death and functional deficits, it can activate neuroprotective mechanisms involving the brain itself as well as remote organs. Within the brain, injured cells and recruited leukocytes can upregulate and/or release paracrine factors and activates resident nerve stem cells, protecting the ischemic cerebrum from injury, enhancing repairing processes, and promoting neuronal regeneration. Cerebral ischemia can also activate intersystem responses, such as upregulation and release of secretory proteins from the liver, to enhance neuronal protection. These naturally evolved mechanisms provide a foundation for developing brain therapeutic strategies. The objectives of this investigation are to evaluate a novel intersystem neuroprotective mechanism: trefoil factor 3 (TFF3) upregulation and release from the liver for neuroprotection and develop a molecular engineering approach for neuroprotection based on such an innate mechanism. In particular, we will evaluate the pathogenic mechanisms of ischemic cerebral calcification, a pathological process involving deposition of the calcium-binding molecules annexins; access the role of TFF3 in mitigating cerebral calcification by blocking annexin deposition; and establish neuroprotective engineering strategies based on the mechanism of annexin and TFF3 action. These studies will establish a basis for future preclinical and clinical research. We will also establish a didactic model to enhance the impact of Regenerative Engineering education by integrating independent research projects into lecture topics, demonstrate the effectiveness of this approach for creativity training, and disseminate the model to national and international Biomedical Engineering Programs. The didactic research will establish a course model that enhances the impact of Biomedical Engineering education.
|Effective start/end date||9/1/14 → 8/31/20|
- National Science Foundation (CBET-1403036)
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