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Updated: Oct 26, 2025
An In Vivo Assessment of Blood-Brain Barrier Disruption in a Rat Model of Ischemic Stroke
Published on: March 11, 2018
Protective effects of Dimethyl malonate on neuroinflammation and blood-brain barrier after ischemic stroke
Zhen Zhang1, Zhengfang Lu1, Chang Liu1
1Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University.
Objectives:
After ischemic stroke, microglia will be activated and play a key role in neuroinflammation and the destruction of the blood-brain barrier (BBB), and activated microglia could polarize into pro-inflammation M1 phenotype and anti-inflammation M2 phenotype. Dimethyl malonate (DMM) could reduce reactive oxygen species and we speculate DMM could regulate microglia to protect ischemic brain.
Methods:
We used transient middle cerebral artery occlusion (tMCAO) mouse model to simulate ischemic stroke and adult male C57BL/6 mice were used in our study. 2,3,5-triphenyltetrazolium chloride staining was used to measure infarct volume. Evans Blue and Brain water content were used to evaluate the destruction of BBB. We used a five-point scale to assess the neurologic function of mice. Western blot and Immunofluorescence were used to measure microglia, pericytes and the expression of related proteins.
Results:
DMM reduced cerebral infarct volume, Evans blue leakage, brain water content and improved neurologic deficits after tMCAO. The number of activated microglia and M1 microglia were decreased and the number of M2 microglia and pericytes were increased after DMM treatment. The expression of tumor necrosis factor-α was reduced while protein levels of IL-10 and ZO-1 were increased through DMM treatment.
Conclusions:
DMM could regulate activation and polarization of microglia to inhibit neuroinflammation and protect BBB.
Insights
Dimethyl malonate (DMM) protects the ischemic brain by reducing inflammation and preserving the blood-brain barrier (BBB). DMM regulates microglia activation, decreasing harmful M1 phenotypes and increasing beneficial M2 phenotypes.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Microglia activation drives neuroinflammation and blood-brain barrier (BBB) damage post-ischemic stroke.
- Activated microglia can adopt pro-inflammatory M1 or anti-inflammatory M2 phenotypes.
Purpose of the Study:
- To investigate the neuroprotective effects of dimethyl malonate (DMM) in an ischemic stroke model.
- To determine if DMM can modulate microglia polarization and protect the blood-brain barrier.
Main Methods:
- Transient middle cerebral artery occlusion (tMCAO) mouse model of ischemic stroke.
- Assessment of infarct volume, BBB integrity (Evans Blue, brain water content), and neurological function.
- Western blot and immunofluorescence to analyze microglia, pericytes, and protein expression (TNF-α, IL-10, ZO-1).
Main Results:
- DMM treatment significantly reduced infarct volume, BBB leakage, and improved neurological deficits.
- DMM decreased M1 microglia and increased M2 microglia and pericyte numbers.
- DMM downregulated TNF-α and upregulated IL-10 and ZO-1 expression.
Conclusions:
- Dimethyl malonate (DMM) demonstrates neuroprotective effects in ischemic stroke.
- DMM regulates microglia activation and polarization, inhibiting neuroinflammation and protecting the BBB.
