Related Experiment Video
Updated: May 10, 2026

Quantification of Neurovascular Protection Following Repetitive Hypoxic Preconditioning and Transient Middle Cerebral Artery Occlusion in Mice
Published on: May 4, 2015
Aging Intensifies Myeloperoxidase Activity after Ischemic Stroke
Negin Jalali Motlagh1,2, Cuihua Wang1,2, Hyung-Hwan Kim3
1Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02114, USA.
Abstract:
Abnormally elevated oxidative stress underlies many diseases and contributes to aging. The myeloid enzyme myeloperoxidase (MPO) generates oxidative stress and contributes to damage after stroke. How aging changes MPO in stroke has not been studied. We aimed to determine the effects aging has on MPO and how these changes contribute to age-related differences in outcomes after ischemic stroke. To investigate tissue MPO activity we developed MPO Activatable Fluorescent Agent (MAFA). We found that aged mice exhibited worse neurological outcomes and higher mortality within the first few days after stroke. Accordingly, neuronal loss was higher in aged mice on day 3. MAFA imaging revealed that aged brains have markedly higher MPO activity that increased after stroke on day 3 compared to young adult brains. Correspondingly, we found more Iba1+ cells in aged brains compared to young adult brains before and after stroke. Interestingly, we found decreased percentage of MPO+ cells and lower MPO protein levels in aged on day 3, suggesting that most Iba1+ cells in aged mice have degranulated and secreted MPO in response to stroke. By day 10 MPO activity and Iba1+ cells decreased in both age groups, although MPO activity remained higher in aged mice. MPO inhibition in aged mice decreased MAFA signal and Iba1+ cells and improved neurobehavioral outcomes to near young adult stroke mice levels and improved mortality rate. While aging is an unmodifiable risk, by uncovering the connection between aging and MPO-related changes after stroke, new therapies can be developed to mitigate these adverse changes brought upon by aging.
Insights
Aging exacerbates stroke damage by increasing myeloperoxidase (MPO) activity in the brain. Inhibiting MPO in aged mice improved neurological outcomes, suggesting new therapeutic targets for stroke patients.
Area of Science:
- Neuroscience
- Immunology
- Aging Research
Background:
- Oxidative stress is implicated in aging and diseases like stroke.
- Myeloperoxidase (MPO) is a myeloid enzyme that generates oxidative stress and contributes to stroke damage.
- The impact of aging on MPO activity and stroke outcomes remains understudied.
Purpose of the Study:
- To investigate how aging affects MPO activity after ischemic stroke.
- To determine the role of MPO in age-related stroke outcomes.
- To explore MPO inhibition as a potential therapeutic strategy for aged stroke patients.
Main Methods:
- Development and utilization of MPO Activatable Fluorescent Agent (MAFA) for imaging.
- Comparison of stroke outcomes, mortality, and neuronal loss in young adult versus aged mice.
- Assessment of MPO activity, Iba1+ cell counts, and MPO protein levels at different time points post-stroke.
- Evaluation of the effects of MPO inhibition on neurobehavioral outcomes and mortality in aged mice.
Main Results:
- Aged mice exhibited worse neurological outcomes, higher mortality, and increased neuronal loss after stroke compared to young adult mice.
- MAFA imaging revealed significantly higher MPO activity in aged brains post-stroke.
- Aged brains showed increased Iba1+ cells, with a decreased percentage of MPO+ cells, suggesting MPO release.
- MPO inhibition in aged mice improved neurobehavioral outcomes and reduced mortality.
Conclusions:
- Aging significantly increases MPO activity and exacerbates stroke-induced brain damage.
- MPO plays a critical role in the adverse outcomes observed in aged individuals following ischemic stroke.
- Targeting MPO activity presents a promising therapeutic avenue to mitigate age-related stroke complications.
Related Concept Videos
Ischemic Stroke l: Introduction
Ischemic Stroke ll: Pathophysiology
Hemorrhagic Stroke l: Introduction
Hemorrhagic Stroke ll: Pathophysiology

