Leader: Giacinto Bagetta (UNICAL); Other collaborator(s):
Aging is associated with increased prevalence of stroke and vascular dementia, while age-related alterations of the immunological response to stroke underlie poor histopathological and functional outcomes in older patients. We will characterize mechanisms implicated in senescence of innate immune cells (microglia/macrophages and neutrophils) that impair their ability to exert regenerative functions. We aim at blocking inflammaging through efficient brain delivery (i.e., nanocarriers) of immunomodulatory tools (azithromycin, miRNAs, etc) to reduce histopathological, motor and cognitive impairments caused by stroke. This approach can be extended to other neurodegenerative conditions to reduce their impact in aging population.
Brief description of the activities and of the intermediate results: After the recruitment of a PhD student, the experimental planning was coordinated within the participating researchers. The nanocarrier design for enhance BBB crossing of miRNAs was theoretically developed. Concomitantly, the experimental protocol for miRNA extraction from brain and plasma was established. Moreover, reliable controls for miRNA detection were identified.
Brief description of the activities and of the intermediate results: Identification of specific miRNA modulated by ischemia-reperfusion injury following temporary blockage of middle cerebral artery in plasma and leukocytes of mice models.
Brief description of the activities and of the intermediate results: Correlation analysis of modulated miRNAs in the plasma of mice subjected to ischemia-reperfusion with brain damage, neurological deficits, and the immune response caused by the insult.
The results of the pilot phase of the BRAINAID randomized placebo-controlled trial with NanoBEO in patients with severe dementia have been published.
Brief description of the activities and of the intermediate results: Identification of the implication of Tumor necrosis factor-stimulated gene-6 (TSG6) in neuroprotection exerted by cerebral ischemic preconditioning in mice subjected to transient middle cerebral artery occlusion.
Scientific papers:
Abstract to national/international conferences:
- Chiara Di Santo, Giacinto Bagetta, Diana Amantea. Tumor necrosis factor-stimulated gene-6 (TSG6) is implicated in neuroprotection exerted by cerebral ischemic preconditioning in mice subjected to transient middle cerebral artery occlusion. 5th International Symposium on Conditioning Medicine: Brain and Heart Medicine