How diesel fumes and low brain blood flow harm white matter
Synergistic white matter injury from diesel exhaust particulate and chronic cerebral hypoperfusion exposures: Interaction between the Nogo/NgR1 receptor pathway and extravascular fibrinogen toxicity
This work looks at how breathing diesel exhaust and having long-term reduced blood flow to the brain together damage white matter and raise dementia risk for people with cerebrovascular problems.
Quick facts
| Grant type | NIH-funded research |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Southern California NIH-funded |
| Lab location | 1 site (Los Angeles, UNITED STATES) |
| Project ID | NIH-10795775 on NIH RePORTER |
What this research studies
Researchers use cell cultures and a mouse model that mimics chronic low brain blood flow to isolate how diesel exhaust particulate (DEP) and chronic cerebral hypoperfusion (CCH) interact to injure white matter. They focus on the Nogo/NgR1 pathway that blocks axon regrowth and on how leaked fibrinogen from a leaky blood-brain barrier worsens damage. Experiments test the independent and combined effects of DEP and CCH and whether targeting NgR1 or the 67 kDa laminin receptor can reduce white matter injury. The goal is to identify mechanisms that could become targets for treatments to protect or repair brain connections affected by pollution and poor blood flow.
Who could benefit from this research
Good fit: Ideal candidates for related future trials would be older adults with cerebrovascular disease, chronic low brain perfusion, or early Alzheimer-type symptoms who have had significant air pollution exposure.
Not a fit: People whose dementia is driven mainly by non-vascular genetic causes or who lack cerebrovascular risk factors are less likely to benefit from these findings.
Why it matters
Potential benefit: If successful, this work could point to new targets to protect or repair white matter and lower dementia risk linked to air pollution and poor brain blood flow.
How similar studies have performed: Prior mouse studies show that particulate exposure and chronic hypoperfusion can combine to worsen white matter injury, but targeting NgR1 and fibrinogen is a relatively new, largely preclinical approach.
Where this research is happening
Los Angeles, UNITED STATES
- University of Southern California — Los Angeles, United States (Active)
Researchers
- Principal investigator: Mack, William J — University of Southern California
- Study coordinator: Mack, William J
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 below.