Impact of Air Pollution on Cerebrovascular Disease: An Evolving Paradigm

Introduction

Hemorrhagic and ischemic strokes can occur as a result of a variety of underlying pathologies and are associated with significant morbidity and mortality. In the acute setting, the focus in ischemic stroke is primarily on revascularization, whereas, in hemorrhagic stroke, the focus is on preventing secondary cerebral injury from local mass effect, increased intracranial pressures, or repeat hemorrhages. Efforts to understand and modify the risk factors for strokes depend on the pathology (i.e., lipid level correction or revascularization procedures to prevent ischemic strokes; blood pressure control to prevent hypertensive hemorrhages; treatment of high-risk aneurysms/vascular malformations to prevent lesional hemorrhages) but are largely predicated on an awareness of these risk factors in the first place. The impact of population-level environmental exposures on stroke risk is often less emphasized because they are harder to modify.

Exposure to airborne pollutants, especially smaller particulate matter able to penetrate tissues deeply (i.e., 2.5 micrometers or smaller; PM2.5), can detrimentally impact a wide range of organ systems and cause respiratory, cardiovascular, and neurologic diseases.¹ Mechanistically, these effects are mediated via multiple pathways, including the induction of local and systemic inflammatory and cytokine cascades leading to DNA damage and cellular death from oxidative stress and immune toxicity.¹ Endothelial cells are particularly affected by PM2.5 exposure, with secondary
inflammatory cascades likely to contribute to systemic atherogenesis and diminished overall vascular health. Although endothelial cell dysfunction is a key mediator of cerebrovascular disease of all types, the impact of PM2.5 exposure on stroke risk appears to be pathology dependent.

Impact of PM2.5 Exposure on Ischemic and Hemorrhagic Stroke

In a recent review of the literature, Kulick et al.² examined the published data on the risk of short- and long-term exposure to ambient air pollution on ischemic and hemorrhagic strokes. Acknowledging the challenges of disentangling the effects of individual pollutant exposures in epidemiologic studies, as well as variations in data based on the country studied and baseline levels of pollution, they report an overall causative relationship between short- and longterm PM2.5 exposure and ischemic stroke risk, without a similarly clear effect by other airborne pollutants such as PM10, nitrogen dioxide, and ozone.² Conversely, data linking the risk of hemorrhagic stroke to either short- or long-term PM2.5 (or other particulate) exposure are more variable,^2,3 potentially reflective of the more heterogenous etiology of hemorrhagic stroke (e.g., hypertensive, amyloid), or a more nuanced relationship between local vessel health, coexisting pathologic conditions, and exposure-related variables.

Novel Link Between PM2.5 Exposure and Intracranial Aneurysm Rupture

Although there is increasing evidence linking local inflammation and risk of intracranial aneurysm formation and rupture,⁴ a link between aneurysmal subarachnoid hemorrhage (aSAH) and PM2.5 exposures had not been found until recently.³ Leveraging cyclic PM2.5 fluctuations from wildfire smoke and local pollutants along Utah’s Wasatch Front, Bounajem et al.⁵ performed a retrospective single-center analysis of 70 patients with aSAH over a 5-year period and reported a delayed positive association between elevated PM2.5 levels and aSAH risk (incident risk ratio 2.03, 95% CI 1.05–3.93, p = 0.035, with PM2.5 spikes occurring 90–180 days prior to hemorrhage spikes). This was the first reported link between PM2.5 exposure and risk of aSAH, and the delayed impact fits with a potentially synergistic downstream effect of systemic cytokine and inflammatory cascades initiated by PM2.5 exposures. These cascades may then amplify local endothelial cell inflammation and accumulation of DNA-level damage from oxidative stress and impairment of repair processes, leading to aneurysmal wall fragility and ultimately rupture. Although additional work is needed to confirm this mechanistic link, this prolonged timescale effect, although initially surprising, is analogous to other longer-term effects of PM2.5 exposures, such as an increased cancer risk that is likely a result of reactive oxygen species formation and DNA damage.¹

Implications and Future Directions

Our increasing understanding of the effects of airborne particulate exposure on cerebrovascular disease presents opportunities for both patient- and population-level action. Further defining the risk of PM2.5 and other particulate exposure on ischemic and hemorrhagic stroke, as well as the exact mechanisms of action are important next steps to better inform and treat patients affected by these diseases. Exposure reduction strategies, such as staying indoors, using N95 masks outdoors, or avoiding strenuous outdoor activities during periods of high PM2.5 levels, could be considered, especially in at-risk patients. On a population level, physician and health-system awareness and advocacy will be critical to the success of public health measures to combat air pollution.

Conclusion

The evidence linking airborne particulate exposure to ischemic stroke, and increasingly hemorrhagic stroke, highlights a need for ongoing epidemiologic and mechanistic study, as well as opportunities for neurosurgical advocacy.

References

1. Sangkham S, Phairuang W, Sherchan SP, et al. An update on adverse health effects from exposure to PM2.5. Environ Adv. 2024;18:100603.
2. Kulick ER, Kaufman JD, Sack C. Ambient air pollution and stroke: an updated review. Stroke. 2023;54(3):882-893.
3. Czernych R, Kozera G, Badyda AJ, Bieniaszewski L, Zagożdżon P. Air pollution increases risk of occurrence of intracerebral haemorrhage but not of subarachnoid haemorrhage: time-series cross-sectional study. Biomedicines. 2024;12(7):1562.
4. Wang J, Wei L, Lu H, Zhu Y. Roles of inflammation in the natural history of intracranial saccular aneurysms. J Neurol Sci. 2021;424:117294
5. Bounajem MT, Brandel MG, Nadel JL, et al. Effects of airborne particulate exposure on aneurysmal subarachnoid hemorrhage risk: brief communication. npj Clean Air. 2025;1(1):18.