# Aging-associated changes in the brain's response after a cardiac arrest

> **NIH NIH K08** · UNIVERSITY OF COLORADO DENVER · 2024 · $224,424

## Abstract

Project Summary/Abstract
The goal of this Mentored Career Development Award is to facilitate the primary investigator's transition to
independence as a physician-scientist studying the molecular mechanisms underlying brain injury that occurs
after a cardiac arrest. The candidate is a MD/PhD critical care physician and anesthesiologist with a
background in neurodegenerative and brain injury research. The award will help the candidate gain research
experience in the analysis of neuronal cell death pathways and brain inflammation, measurement of synaptic
function, and assessment of cognition in mouse models of cardiac arrest. The environment in which the
proposed research will be conducted is outstanding, and includes structured mentorship from neuroscientists
and physician-scientists with diverse backgrounds. The candidates mentor and co-mentor, Dr. Nidia Quillinan
and Dr. Elizabeth J. Kovacs, are well-respected experts in the fields of cardiac arrest, global cerebral ischemia,
aging research, and inflammation. The proposed research will investigate the role of inflammasome pathways
as molecular mediators of age-related differences in brain injury after global cerebral ischemia induced by a
cardiac arrest. The incidence of cardiac arrest dramatically increases with age, with older survivors having a
worse neurologic prognosis and poor response to post-arrest care. A potential cause of worsening brain
dysfunction after a cardiac arrest in older individuals is age-associated inflammation (inflammaging). Activation
of the inflammasome multi-protein complex is a primary driver of inflammaging and has been shown to mediate
cognitive deficits in both brain injury and disease. The goal of this project is to test the hypothesis that global
cerebral ischemia results in a more robust and sustained inflammasome activation with advanced age that
results in increased cell death and synaptic deficits in survivors. In order to test this hypothesis, the primary
investigator will use a murine model of cardiac arrest and cardiopulmonary resuscitation (CA/CPR) to (Aim 1)
assess for age-related differences in inflammasome-mediated inflammation after global cerebral ischemia and
(Aim 2) evaluate the extent to which inflammasome activity contributes to CA/CPR induced neuronal cell loss,
acute deficits in synaptic function, and cognitive impairment in young and advanced age mice. The proposed
experiments are designed to elucidate a novel aging-relevant molecular mechanism involved in the brain's
response to global cerebral ischemia. This career development award will provide the primary investigator with
valuable research training relevant to the realms of ischemia, aging biology, and inflammation that will
complement his clinical management of cardiac arrest survivors in the intensive care unit, and ultimately
provide a skill set for the translation of basic science discoveries into novel therapeutic strategies for patients
that suffer a cardiac arrest.

## Key facts

- **NIH application ID:** 10984378
- **Project number:** 1K08NS135129-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Jacob Basak
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $224,424
- **Award type:** 1
- **Project period:** 2024-08-15 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10984378

## Citation

> US National Institutes of Health, RePORTER application 10984378, Aging-associated changes in the brain's response after a cardiac arrest (1K08NS135129-01A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10984378. Licensed CC0.

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