Related Experiment Video
Updated: Jun 26, 2025
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
DCPIB Attenuates Ischemia-Reperfusion Injury by Regulating Microglial M1/M2 Polarization and Oxidative Stress
Guihua Cao1, Jianbin Guo2, Kaikai Yang1
1Department of Geriatrics, Xijing Hospital of Air Force Military Medical University, Xi'an 710032, China.
Abstract:
The inflammatory response plays an indispensable role in ischemia-reperfusion injury, the most significant of which is the inflammatory response caused by microglial polarization. Anti-inflammatory therapy is also an important remedial measure after failed vascular reconstruction. Maintaining the internal homeostasis of the brain is a crucial measure for suppressing the inflammatory response. The mechanism underlying the relationship between DCPIB, a selective blocker of volume-regulated anion channels (VRAC), and inflammation induced by cerebral ischemia-reperfusion injury is currently unclear. The purpose of this study was to investigate the relationship between DCPIB and microglial M1/M2 polarization-mediated inflammation after cerebral ischemia-reperfusion injury. C57BL/6 mice were subjected to transient middle cerebral artery occlusion (tMCAO). DCPIB was administered by a lateral ventricular injection within 5 min after reperfusion. Behavioral assessments were conducted at 1, 3, and 7 days after tMCAO/R. Pathological injuries were evaluated using TTC assay, HE and Nissl staining, brain water content measurement, and immunofluorescence staining. The levels of inflammatory cytokines were analyzed using qPCR and ELISA. Additionally, the phenotypic variations of microglia were examined using immunofluorescence staining. In mouse tMCAO/R model, DCPIB administration markably reduced mortality, improved behavioral performance, and alleviated pathological injury. DCPIB treatment significantly inhibited the inflammatory response, promoted the conversion of M1 microglia to M2 microglia via the MAPK signaling pathway, and ultimately protected neurons from the microglia-mediated inflammatory response. In addition, DCPIB inhibited oxidative stress induced by cerebral ischemia-reperfusion injury. In conclusion, DCPIB attenuates cerebral ischemia-reperfusion injury by regulating microglial M1/M2 polarization and oxidative stress.
Insights
DCPIB, a volume-regulated anion channel blocker, reduces brain damage after stroke by shifting microglia from inflammatory M1 to healing M2 states. This anti-inflammatory action also combats oxidative stress, improving outcomes in cerebral ischemia-reperfusion injury.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Inflammatory responses, particularly microglial polarization, are critical in ischemia-reperfusion injury (IRI).
- Anti-inflammatory therapies are vital for managing failed vascular reconstruction and brain homeostasis.
- The role of DCPIB, a volume-regulated anion channel (VRAC) blocker, in cerebral IRI-induced inflammation remains unclear.
Purpose of the Study:
- To investigate the relationship between DCPIB and inflammation mediated by microglial M1/M2 polarization following cerebral IRI.
- To elucidate DCPIB's mechanism in mitigating neuroinflammation and neuronal damage.
Main Methods:
- Transient middle cerebral artery occlusion (tMCAO) model in C57BL/6 mice.
- DCPIB administration via lateral ventricular injection post-reperfusion.
- Assessment of behavioral deficits, pathological injury (TTC, HE, Nissl, brain water content), inflammatory cytokine levels (qPCR, ELISA), and microglial phenotypes (immunofluorescence).
Main Results:
- DCPIB administration significantly reduced mortality, improved behavioral performance, and alleviated brain injury in the tMCAO model.
- DCPIB treatment inhibited inflammatory responses and promoted M1 to M2 microglial polarization via the MAPK signaling pathway.
- DCPIB also suppressed oxidative stress, offering neuroprotection against IRI.
Conclusions:
- DCPIB attenuates cerebral IRI by modulating microglial M1/M2 polarization and reducing oxidative stress.
- DCPIB demonstrates therapeutic potential for treating stroke and related neurological conditions.
- Targeting VRAC with DCPIB offers a novel strategy for managing neuroinflammation post-stroke.
