Related Experiment Video
Updated: Dec 28, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Modulation of Microglia Polarization through Silencing of NF-κB p65 by Functionalized Curdlan Nanoparticle-Mediated
Tsogzolmaa Ganbold1,2, Qingming Bao1, Jargalmaa Zandan1
1Institute of Mongolian Medicinal Chemistry, School of Chemistry & Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia 010020, P. R. China.
Abstract:
Microglia polarization plays an important role in poststroke recovery. Inhibition of proinflammatory (M1) polarization and promotion of anti-inflammatory (M2) polarization of microglia are potential therapeutic strategies for inflammation reduction and neuronal recovery after stroke. Here, we evaluated the central nervous system (CNS)-targeted short interfering RNA (siRNA) delivery ability of functionalized curdlan nanoparticles (CMI) and investigated the nuclear factor-κB (NF-κB) p65 silencing efficiency of CMI-mediated siRNA in microglia, as well as the resulting neuroprotective effect of microglia polarization and neuroprotection in vitro and in vivo. The systemic delivery of NF-κB p65 siRNA (sip65) complexed to CMI nanoparticles in the mouse model of transient middle cerebral artery occlusion (tMCAO) resulted in the distribution of siRNA in microglia and significant silencing in NF-κB p65 in the peri-infarct region. Knockdown of NF-κB p65 resulted in M1 to M2 phenotypic transition of microglia, evidenced by the change in the expression pattern of signature cytokines as well as inducible nitric oxide synthase and CD206. Moreover, the CMI-mediated silencing of p65 increased the density of neurons and decreased pyknosis and edema in the peri-infarct region. Assessment of the neurological deficit score on the Bederson scale revealed a significantly reduced score in the mouse model of tMCAO treated with the sip65/CMI complex. Collectively, our data suggest that CMI nanoparticles are a promising CNS-targeting siRNA delivery system, and NF-κB p65 may be a potential therapeutic target for inflammation reduction and poststroke recovery.
Insights
Functionalized curdlan nanoparticles effectively deliver siRNA to microglia, reducing inflammation and promoting recovery after stroke by targeting NF-κB p65. This approach aids neuronal survival and neurological function.
Area of Science:
- Neuroscience
- Biotechnology
- Pharmacology
Background:
- Microglia polarization is crucial for post-stroke recovery, with M1 (proinflammatory) and M2 (anti-inflammatory) phenotypes influencing outcomes.
- Targeting microglia polarization offers a therapeutic strategy for reducing inflammation and enhancing neuronal repair following stroke.
Purpose of the Study:
- To evaluate curdlan nanoparticles (CMI) for central nervous system (CNS)-targeted delivery of short interfering RNA (siRNA).
- To investigate the efficacy of CMI-mediated siRNA targeting nuclear factor-κB (NF-κB) p65 in microglia.
- To assess the neuroprotective effects of NF-κB p65 silencing on microglia polarization and neuronal survival in vitro and in vivo.
Main Methods:
- Systemic administration of NF-κB p65 siRNA (sip65) complexed with CMI nanoparticles in a mouse model of transient middle cerebral artery occlusion (tMCAO).
- Analysis of siRNA distribution in microglia and NF-κB p65 silencing in the peri-infarct region.
- Evaluation of microglia polarization markers (cytokines, iNOS, CD206), neuronal density, pyknosis, edema, and neurological deficit scores (Bederson scale).
Main Results:
- CMI nanoparticles successfully delivered sip65 to microglia in the peri-infarct area, leading to significant NF-κB p65 silencing.
- Knockdown of NF-κB p65 induced a shift from M1 to M2 microglia polarization.
- Treatment with sip65/CMI complex increased neuronal density, reduced neuronal damage and edema, and improved neurological function in tMCAO mice.
Conclusions:
- CMI nanoparticles represent a promising siRNA delivery system for CNS applications, particularly for stroke treatment.
- NF-κB p65 is a viable therapeutic target for modulating microglia polarization and promoting neuroprotection and recovery after stroke.
Related Concept Videos
02:26NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...
02:15Experimental RNAi