Effects of hydrogel microspheres loaded with interleukin-4 on neural functional recovery by modulating the immune microenvironment after stroke

doi:10.3969/j.issn.1674-8115.2025.09.008

Abstract

Abstract:

Objective ·To explore the effects of hydrogel microsphere (MP) loaded with the immunoregulatory factor interleukin-4 (IL-4) on the regeneration and repair after stroke injury. Methods ·IL-4-loaded nanoparticles were prepared using an emulsification method and subsequently incorporated into polyvinyl alcohol (PVA) hydrogel microspheres via an airflow technique to obtain IL-4-loaded PVA hydrogel microspheres (MP@IL-4). The morphology of MP@IL-4 was characterized by optical microscopy. BV2 microglia were cultured in vitro and treated with MP@IL-4. Cell viability and survival were detected by the CCK-8 assay and live/dead cell staining, respectively. Subsequently, BV2 microglia were further treated with lipopolysaccharide (LPS), and the expression levels of the pro-inflammatory marker inducible nitric oxide synthase (iNOS) and the anti-inflammatory marker arginase 1 (Arg-1) were detected by immunofluorescence staining. Meanwhile, a mouse stroke model was constructed using the middle cerebral artery occlusion method, and the mice were randomly divided into the sham operation group (Sham group), the ischemic stroke (IS) group and the microsphere treatment group (IS-MP@IL-4 group). The neurobehavioral functions of mice in the three groups were detected by the modified Neurological Severity Score, elevated body swing test, and hanging wire test. The brain atrophy volume was detected by cresyl violet staining. Immunofluorescence staining was used to assess the expression levels of the pro-inflammatory factor CD86 and the anti-inflammatory factor CD206 in microglia. Results ·Optical microscopy confirmed the successful fabrication of MP@IL-4 with a particle size of 200 μm, which did not affect the cell viability and survival of BV2 microglia. Both in vitro and in vivo experiments demonstrated that MP@IL-4 downregulated the expression of pro-inflammatory markers and upregulated the expression of anti-inflammatory markers in microglia. Moreover, compared with the IS group, the neurobehavioral function of mice in the IS-MP@IL-4 group was significantly improved (P<0.05), and the brain atrophy volume was reduced (P<0.001). Conclusion ·MP@IL-4 can exert a therapeutic effect on post-stroke neurofunctional injury by improving the immune microenvironment.

Key words: hydrogel microsphere, drug delivery, ischemic stroke (IS), anti-inflammatory effect, neural repair

CLC Number:

R743

XU Tongtong, RUAN Huitong. Effects of hydrogel microspheres loaded with interleukin-4 on neural functional recovery by modulating the immune microenvironment after stroke[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025, 45(9): 1161-1170.

Figures/Tables 5

Fig 1 Characterization and release profile of MP@IL-4

Fig 2 Analysis of proliferation and viability of BV2 microglia

Fig 3 Effect of MP@IL-4 on the polarization level of BV2 microglia in vitro (×100)

Fig 4 Effects of MP@IL-4 on the neural functional recovery of IS mice

Fig 5 Effects of MP@IL-4 on the polarization level of mouse microglia (×200)

TrendMD

References 36

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