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Updated: Jan 25, 2026
Optimized Management of Endovascular Treatment for Acute Ischemic Stroke
Published on: January 18, 2018
Role of acute-phase protein ORM in a mice model of ischemic stroke
Jing-Jing Wan1,2, Peng-Yuan Wang2, Yu Zhang2
1Department of Clinical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai, 200433, China.
Abstract:
The only Food and Drug Administration-approved treatment for acute ischemic stroke is tissue plasminogen activator, and the discovery of novel therapeutic targets is critical. Here, we found orosomucoid (ORM), an acute-phase protein mainly produced by the liver, might act as a treatment candidate for an ischemic stroke. The results showed that ORM2 is the dominant subtype in mice normal brain tissue. After middle cerebral artery occlusion (MCAO), the level of ORM2 is significantly increased in the ischemic penumbra compared with the contralateral normal brain tissue, whereas ORM1 knockout did not affect the infarct size. Exogenous ORM could significantly decrease infarct size and neurological deficit score. Inspiringly, the best administration time point was at 4.5 and 6 hr after MCAO. ORM could markedly decrease the Evans blue extravasation, and improve blood-brain barrier-associated proteins expression in the ischemic penumbra of MACO mice and oxygen-glucose deprivation (OGD)-treated bEnd3 cells. Meanwhile, ORM could significantly alleviate inflammation by inhibiting the production of interleukin 1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α), reduce oxidative stress by improving the balance of malondialdehyde (MDA) and superoxide dismutase (SOD), inhibit apoptosis by decreasing caspase-3 activity in ischemic penumbra of MCAO mice and OGD-treated bEnd.3 cells. Because of its protective role at multiple levels, ORM might be a promising therapeutic target for ischemic stroke.
Insights
Orosomucoid (ORM) shows promise as a novel therapeutic for acute ischemic stroke. Administering ORM after stroke significantly reduced brain infarct size and improved neurological function by protecting the blood-brain barrier and reducing inflammation.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Tissue plasminogen activator is the sole FDA-approved treatment for acute ischemic stroke, highlighting the urgent need for novel therapeutic targets.
- Orosomucoid (ORM), an acute-phase protein primarily synthesized in the liver, is investigated for its potential therapeutic role in ischemic stroke.
Purpose of the Study:
- To evaluate orosomucoid (ORM) as a potential therapeutic candidate for acute ischemic stroke.
- To investigate the effects of ORM on brain tissue, blood-brain barrier integrity, inflammation, oxidative stress, and apoptosis following ischemic events.
Main Methods:
- Middle cerebral artery occlusion (MCAO) model in mice to induce ischemic stroke.
- Assessment of ORM2 levels in ischemic penumbra and contralateral brain tissue.
- Administration of exogenous ORM and evaluation of infarct size, neurological deficit scores, Evans blue extravasation, and expression of blood-brain barrier-associated proteins.
- In vitro studies using oxygen-glucose deprivation (OGD)-treated bEnd.3 cells to assess ORM's effects on inflammation (IL-1β, IL-6, TNF-α), oxidative stress (MDA, SOD), and apoptosis (caspase-3 activity).
Main Results:
- ORM2 was identified as the dominant subtype in normal mouse brain tissue and significantly increased in the ischemic penumbra post-MCAO.
- Exogenous ORM administration significantly reduced infarct size and neurological deficit scores, with optimal timing at 4.5-6 hours post-MCAO.
- ORM treatment decreased Evans blue extravasation, improved blood-brain barrier integrity, alleviated inflammation, reduced oxidative stress, and inhibited apoptosis in both MCAO mice and OGD-treated cells.
Conclusions:
- Orosomucoid (ORM) demonstrates significant neuroprotective effects in experimental models of ischemic stroke.
- ORM acts through multiple mechanisms, including blood-brain barrier stabilization, anti-inflammatory, antioxidant, and anti-apoptotic actions.
- ORM represents a promising therapeutic target for the development of novel treatments for acute ischemic stroke.
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