Influence of thalamic IL-33 signaling in aging-associated exacerbation of cognitive impairment after brain injury via microglial dysfunction and tau pathology

NIH RePORTER · NIH · RF1 · $69,185 · view on reporter.nih.gov ↗

Abstract

Abstract This supplementary award aims to provide extensive research training in neuroimmunology for a gap-year researcher. The proposed project explores the complex landscape of age-associated neutrophil alterations in the brain after cortical brain injuries and clarifies their unique contributions to neuroinflammation and cognitive effects. This investigation focuses on understanding the role of aging-associated neutrophil subpopulations post-injury within the thalamus, leveraging single-cell RNA sequencing (scRNA-seq) data from our parental R01 award. We aim to identify specific age-associated indicators within the brain using refined analysis techniques and advanced clustering algorithms. Validation of the presence and activation status of these markers in the injured brain will be pursued through immunohistochemistry and flow cytometry, providing crucial insights into the nuanced age-specific neutrophil responses. We aim to elucidate the intricate interplay between age-specific neutrophil subpopulations, their activation dynamics, and the evolving neuroinflammatory and cognitive consequences following traumatic brain injury. We will also examine how neuroinflammation and cognitive recovery after injuries are affected by age-associated neutrophil suppression. We will use methods established in our parental R01, particularly antibody-based cell depletion, to assess the impact of age- associated neutrophil infiltration on neuroinflammatory markers, microglial activation, and cognitive recovery after injuries. These studies will be conducted in parallel to hands-on experiments and data analysis training, which will enhance the researcher’s skills and prepare the researcher for graduate studies.

Key facts

NIH application ID
11040248
Project number
3RF1AG079129-01S1
Recipient
UNIVERSITY OF ALABAMA AT BIRMINGHAM
Principal Investigator
Shinichi Kano
Activity code
RF1
Funding institute
NIH
Fiscal year
2024
Award amount
$69,185
Award type
3
Project period
2022-09-15 → 2025-08-31