Neurodegenerative diseases (NDs), considered the 21st-century epidemic, are characterized by brain inflammation. This project aims to leverage recently discovered skull-meninges connections (SMCs) to address this issue. Through tissue-clearing methods, it has been found that the calvaria bone marrow directly connects to brain meninges, suggesting involvement in various brain pathologies. This accessibility makes it attractive for drug delivery and potential biomarker detection. However, detailed SMC and calvaria characteristics and their correlation with neuropathology are unknown. High-throughput technologies will be used to investigate these aspects in ischemic stroke and dementia models, pursuing diagnostic and therapeutic potential. The main objectives are to: 1) Investigate calvaria's molecular, cellular, and structural aspects in physiological states. 2) Explore therapeutic manipulation of calvaria to mitigate stroke and dementia. 3) Develop diagnostic calvaria imaging for stroke and dementia monitoring.
With neurodegenerative diseases being a significant socio-economic burden, this research could yield innovative diagnostic and therapeutic targets, ultimately impacting public health. The project addresses the structural, cellular, and molecular profiles of the calvaria's connection to brain meninges and its potential to manage neuroinflammation. As a pioneering investigation into the impact of the skull on brain function, the study leverages advanced techniques to explore this new avenue of research.