Aging immune reactions to released mitochondria worsen thinking and memory after stroke
Official title: Aging Immunity to Extracellular Mitochondria Exacerbates Vascular Cognitive Impairment After Stroke
Funded at Massachusetts General Hospital · NIH-11330565 · Data updated 2026-11-12
This project explores whether age-related immune changes make mitochondria released after stroke trigger inflammation that worsens thinking and memory in older stroke survivors.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Massachusetts General Hospital NIH-funded |
| Lab location | 1 site (Boston, United States) |
| Project start | May 15, 2025 |
| Project end | March 31, 2030 |
| Funding year | 2026 |
| Award (this year) | $470,786 |
| NIH project number | 5R01NS137979-02 |
| Project ID | NIH-11330565 on NIH RePORTER |
Who could benefit from this research
✓Could help
Older adults who have had a stroke and are experiencing or are at risk for vascular-related thinking and memory problems would be the most relevant candidates.
✕Less likely to help
People without a history of stroke or whose cognitive decline is driven entirely by non-vascular causes are unlikely to gain direct benefit from this work.
What this research studies
From a patient perspective, scientists will compare young and aged brains after stroke to see how immune cells handle mitochondria released from damaged cells. They will use laboratory models of stroke, examine microglia and macrophage recycling pathways (including SQSTM1-LC3-Rab27 and Rab27a), and test what happens when these pathways are blocked. The team will measure tagged mitochondria and complement proteins in blood and spleen samples to link immune changes with worse blood-vessel and brain outcomes. The goal is to find whether restoring protective mitochondrial recycling or blocking harmful immune tagging could reduce vascular-related thinking problems after stroke.
Why it matters
Potential benefit: If successful, the work could point to new ways to prevent or reduce vascular cognitive decline after stroke by restoring protective mitochondrial recycling or blocking harmful immune tagging.
How similar studies have gone: The investigators have pilot animal and cell data supporting this mechanism, but applying this specific mitochondrial–immune link to human patients is a novel step that has not yet been proven.
Where this research is happening
-
Massachusetts General Hospital
Boston, United States Active
Researchers
- Principal investigator: Hayakawa, Kazuhide — Massachusetts General Hospital
- Study coordinator: Hayakawa, Kazuhide
Related research
Other NIH-funded projects on the same topics.
-
How aging affects the immune response to mitochondria after a stroke and its impact on cognitive function
This study looks at how the immune system in older adults reacts to certain cell parts after a stroke and how this might affect thinking and memory, aiming to help us understand why some people have more trouble recovering from a stroke as they age.
-
How biological aging and blood proteins relate to thinking after a stroke
This project looks at whether measures of biological aging and patterns of blood proteins help explain which stroke survivors keep their thinking sharp and which go on to develop vascular dementia.
-
GPR39-based treatment approach for aging-related brain vascular dementia
A new drug-style compound that activates GPR39 in the brain is being studied to help people with vascular dementia linked to aging.
-
Pericyte signaling in diabetic stroke-related cognitive problems
A patient-facing study exploring how blood vessel cells and inflammation after stroke interact in people with diabetes to influence cognitive decline and dementia.
-
Brain networks and reading after stroke and aging
A large study at Georgetown University aims to understand why reading is impaired after stroke and how aging affects reading, using advanced brain imaging to map the networks that support reading.”
-
Thalamic IL-33 signaling and aging-related cognitive decline after brain injury
Aiming to understand how aging and brain injury interact to worsen memory and thinking problems by studying a specific brain signal (IL-33) in the thalamus and its effect on brain immune cells and tau pathology.
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page.