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Original Article
Neuroprotective therapy and visualization of acute ischemic stroke based on inflammation-targeted MRI molecular probe in mice
JIANG Wenhui  HUANG Qinwen  NAN Jin  XIA Chundongqiu  ZHANG Jun 

Cite this article as: JIANG W H, HUANG Q W, NAN J, et al. Neuroprotective therapy and visualization of acute ischemic stroke based on inflammation-targeted MRI molecular probe in mice[J]. Chin J Magn Reson Imaging, 2026, 17(9): 152-161. DOI:10.12015/issn.1674-8034.2026.09.020.


[Abstract] Objective To investigate the role of an inflammation-targeted MRI molecular probe in visualizing neuroinflammation and providing targeted therapy in ischemic stroke.Materials and Methods The inflammation-targeted probe (MA@Z-UMino) was prepared by co-incubating macrophages with Zeolitic Imidazolate Framework-8 (ZIF-8) loaded with minocycline and ultrasmall superparamagnetic iron oxide (USPIO), followed by characterization. A left middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model was established. A total of 100 male C57BL/6 mice aged 8 to 9 weeks were assigned to the normal control group (n=10), Sham group (n=10), and MCAO/R group (n=80). Sixty MCAO/R mice were randomly divided into the MCAO/R, ZIF-8-loaded USPIO (Z-U), minocycline (Mino), macrophage (MA), ZIF-8-loaded USPIO and minocycline (Z-UMino), and MA@Z-UMino groups (n=10 per group). These groups, together with the normal control group and Sham group, were used for therapeutic efficacy evaluation, including 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, inflammatory cytokine analysis, and behavioral and histopathological assessments in selected representative groups. The remaining 20 MCAO/R mice were randomly divided into the Z-UMino and MA@Z-UMino groups (n=10 per group) for in vivo magnetic resonance imaging (MRI). MRI was performed before and at 0.5, 1, and 2 h after injection. The signal-to-noise ratio (SNR) of the brain tissue on the lesion side and its percentage decrease were calculated. Brain specimens were further analyzed pathologically.Results MA@Z-UMino exhibited a predominantly anti-inflammatory phenotype. The transverse relaxation rate of MA@Z-UMino was 17.08 mM-1s-1, indicating its effectiveness for T2-weighted imaging. In vivo MRI showed that the SNR reduction rate of lesion-side brain tissue decreased more obviously in the MA@Z-UMino group than that in the Z-UMino group at 2 h post-treatment (2 h, 31.24 ± 9.30 vs. 15.88 ± 6.79, P < 0.001). Prussian blue staining and immunofluorescence confirmed probe accumulation in the infarct region. Compared with the MCAO/R group, the MA@Z-UMino group showed a significantly smaller infarct area (36.42 ± 5.49 vs. 15.72 ± 4.78, P < 0.001), reduced inflammation, and improved motor function.Conclusions MA@Z-UMino enables targeted recognition of the inflammatory microenvironment in ischemic stroke, MRI-based visualization, and neuroprotective therapy in mice with MCAO/R.
[Keywords] ischemic stroke;mice;macrophages;nanoprobe;molecular imaging;magnetic resonance imaging

JIANG Wenhui   HUANG Qinwen   NAN Jin   XIA Chundongqiu   ZHANG Jun*  

Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200040, China

Corresponding author: ZHANG J, E-mail: zhj81828@163.com

Conflicts of interest   None.

Received  2026-04-12
Accepted  2026-08-21
DOI: 10.12015/issn.1674-8034.2026.09.020
Cite this article as: JIANG W H, HUANG Q W, NAN J, et al. Neuroprotective therapy and visualization of acute ischemic stroke based on inflammation-targeted MRI molecular probe in mice[J]. Chin J Magn Reson Imaging, 2026, 17(9): 152-161. DOI:10.12015/issn.1674-8034.2026.09.020.

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