Research ArticleOriginal Article
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Poloxamer 188 alleviates cerebral ischemia-reperfusion injury in mice by reducing mitochondrial and lysosomal membrane damage

Hui Xu, Zhanhu Zhang, Xiaodong Tao, Ruirui Shi, Jian Xu, Xiaohua Zhang and Jinhua Gu
Neurosciences Journal July 2025, 30 (3) 216-225; DOI: https://doi.org/10.17712/nsj.2025.3.20240025

Article Figures & Data

Figures

  • Figure 1
    Figure 1

    - Tissues for TCC staining and Western blotting.

  • Figure 2
    Figure 2

    - P188 reduced cerebral I/R injury in mice. P188 (0.4 g/kg) or Saline was administered to mice intravenously (i.v.) via tail vein 5 min before reperfusion. 24 h after reperfusion, mice were used for TTC staining, motor deficits and water content analysis. (A) Representative images of TTC staining. Infarct regions of brain displayed white after TTC staining. n=8 in each group. (B) Quantitative analysis of brain infarct volume, which was calculated as percentage of ipsilateral hemisphere. n=8 in each group. (C) Motor deficits of mice 24 h after reperfusion. n=8 in each group. (D) Quantitative analysis of water content. n=8 in each group. *p<0.05 vs. Saline; #p<0.05 vs. sham. Data were presented as mean±SEM.

  • Figure 3
    Figure 3

    - Identification and analysis of P188 labeled by iridium complex. The structure of Iridium complexes (A) and Ir-P188 (B). (C) 1H-NMR spectroscopy of P188 and Ir-P188. The UV-Vis absorption (D) and photoluminescence spectra (E) of Ir-P188 in CHCl3.

  • Figure 4
    Figure 4

    - Distribution of Ir-P188 in the OGD/R–induced HT-22 cell and in brain from mice after ischemic injury. (A, B) Ir-P188 (10-5 M) was added to the OGD/R–induced HT22 cell culture medium, and after 10 min, the distribution of Ir-P188 inside and outside the cells was observed by fluorescence microscope. Distribution of Ir-P188 in the OGD/R–induced HT22 cell. Scale bar=50 µm. Mice was subjected to MCAO for 2 h and 24 h reperfusion, and administered (i.c.v.) with 3µL mixture of PI and Ir-P188 (0.25µg PI dissolved in 1µL 10% Ir-p188). 30 min later the brain was used for fluorescence analysis. (C) Distribution of Ir-P188 in the brain from mice after I/R. Scale bar=50 µm. (D and E) The images were high-magnification for boxes in The images were highmagnification for boxes in (C). Scale bar=20 µm. n=8 in each group.

  • Figure 5
    Figure 5

    - Effects of P188 on inflammatory markers, oxidative stress, and organelle membrane integrity in mice following cerebral I/R injury. (A) 24 h after I/R injury, ischemic cortex was used for western blotting analysis. Cyt C, COX in the mitochondrial and cytosolic fractions were determined. M: mitochondrial fraction; C: cytosol fraction. (B) Cathepsin L, LAMP2 in the lysosome and cytosolic fractions of ischemic cortex were analyzed with western blotting. L: lysosome fraction; C: cytosol fraction. n=8 in each group. (C) Cleaved Caspase 3 expression. (D) NF-κB phosphorylation. n=6 in each group. (E) ROS quantification. (F) TNF-α level (G) IL-6 level. n=3 in each group. *p<0.05, **p<0.01, ***p<0.001 vs. Sham Group; #p<0.05, ##p<0.01, ###p<0.001 vs. Saline Group. Data were presented as mean ± SEM.

  • Figure 6
    Figure 6

    - Neuroprotective effects of combined GB and P188 in mouse model of I/R. P188 (0.4g/kg), GB (20 mg/kg) and mixture were administered after reperfusion. (A) Representative TTC staining sections. (B) Quantitation of infarct volumes. (C) Cerebral water content and (D) Neurological deficits. Data are expressed as mean ± SEM (n=10). *p<0.05, **p<0.01 compared to the saline-treated group, #p<0.05, ##p<0.01 compared to p188+GB group in (B) and compared to Sham group in (C).

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