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Updated: Mar 21, 2026

Assessment of Vascular Regeneration in the CNS Using the Mouse Retina
Published on: June 23, 2014
Aging Inhibits Emergency Angiogenesis and Exacerbates Neuronal Damage by Downregulating DARS2
Dan Liu1, Meilin Weng2, Rui Wang3
1Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, The Heilongjiang Key Laboratory of Anesthesia and Intensive Care Research, Harbin Medical University, Harbin, People's Republic of China.
Background:
Early vascular regeneration is important for the speedy recovery of neurological function following ischemic stroke. M2-like microglia polarization decreases and vascular regeneration weakens with aging. The function of mitochondrial respiratory chain is dependent on M2-like polarization in microglia. DARS2 gene is a marker for mitochondrial respiratory chain function, but its specific molecular mechanism affecting acute angiogenesis of microglia during ischemic stroke in elderly individuals remains unclear.
Methods:
A murine model of middle cerebral artery occlusion (MCAO) was used to perform animal behavioral assessments, immunoblotting, tube formation and chick embryo chorioallantoic membrane assays. A D-galactose-induced cellular senescence model was established in BV2 cells.
Results:
Aging significantly exacerbates acute brain injury 24 hours post-cerebral ischemia-reperfusion, with increased expression of M1-like microglial markers and a concomitant decrease in M2-like microglial markers. Additionally, aging can inhibit DARS2 protein expression, adversely affect angiogenesis and reduce brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor A (VEGFA) expression. In vitro, oxygen-glucose deprivation/reoxygenation and re-glucose (OGD/R) demonstrated that DARS2 gene knockout in young microglia replicates the phenotypic characteristics observed in aged microglia.
Conclusion:
This study suggests that aging impedes M2-like microglial polarization by downregulating DARS2 expression in microglia, thereby impairing emergency angiogenesis during acute ischemic stroke and exacerbating neuronal damage.
Insights
Aging impairs microglial function and blood vessel repair after stroke by reducing DARS2 expression. This leads to worse brain injury in older individuals, highlighting DARS2's role in recovery.
Area of Science:
- Neuroscience
- Vascular Biology
- Aging Research
Background:
- Early vascular regeneration is crucial for neurological recovery after ischemic stroke.
- Aging is associated with decreased M2-like microglia polarization and weakened vascular regeneration.
- The DARS2 gene, a marker for mitochondrial function, plays a role in M2-like microglia polarization, but its mechanism in aging stroke is unclear.
Purpose of the Study:
- To investigate the molecular mechanism of DARS2 in microglia-mediated angiogenesis during acute ischemic stroke in elderly individuals.
- To elucidate the impact of aging on DARS2 expression and its subsequent effects on vascular regeneration and neurological function.
Main Methods:
- Utilized a murine model of middle cerebral artery occlusion (MCAO) for in vivo studies.
- Performed behavioral assessments, immunoblotting, and angiogenesis assays (tube formation, chick embryo chorioallantoic membrane).
- Established a D-galactose-induced cellular senescence model in BV2 microglia.
Main Results:
- Aging exacerbated acute brain injury post-ischemia-reperfusion, characterized by M1/M2 microglia imbalance and reduced DARS2 protein expression.
- Aging inhibited angiogenesis and decreased expression of BDNF and VEGFA.
- DARS2 gene knockout in young microglia mimicked aged microglia phenotypes in vitro.
Conclusions:
- Aging impedes M2-like microglial polarization by downregulating DARS2 expression.
- This downregulation impairs emergency angiogenesis in acute ischemic stroke, leading to increased neuronal damage.
- DARS2 is a key factor in age-related decline of microglial function and vascular repair post-stroke.
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