Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun;16(3):645-654.
doi: 10.1007/s12975-024-01241-0. Epub 2024 Mar 15.

Experimental Ischemic Stroke Induces Secondary Bihemispheric White Matter Degeneration and Long-Term Cognitive Impairment

Affiliations

Experimental Ischemic Stroke Induces Secondary Bihemispheric White Matter Degeneration and Long-Term Cognitive Impairment

Ran Liu et al. Transl Stroke Res. 2025 Jun.

Abstract

Clinical studies have identified widespread white matter degeneration in ischemic stroke patients. However, contemporary research in stroke has predominately focused on the infarct and periinfarct penumbra regions. The involvement of white matter degeneration after ischemic stroke and its contribution to post-stroke cognitive impairment and dementia (PSCID) has remained less explored in experimental models. In this study, we examined the progression of locomotor and cognitive function up to 4 months after inducing ischemic stroke by middle cerebral artery occlusion in young adult rats. Despite evident ongoing locomotor recovery, long-term cognitive and affective impairments persisted after ischemic stroke, as indicated by Morris water maze, elevated plus maze, and open field performance. At 4 months after stroke, multimodal MRI was conducted to assess white matter degeneration. T2-weighted MRI (T2WI) unveiled bilateral cerebroventricular enlargement after ischemic stroke. Fluid Attenuated Inversion Recovery MRI (FLAIR) revealed white matter hyperintensities in the corpus callosum and fornix across bilateral hemispheres. A positive association between the volume of white matter hyperintensities and total cerebroventricular volume was noted in stroke rats. Further evidence of bilateral white matter degeneration was indicated by the reduction of fractional anisotropy and quantitative anisotropy at bilateral corpus callosum in diffusion-weighted MRI (DWI) analysis. Additionally, microglia and astrocyte activation were identified in the bilateral corpus callosum after stroke. Our study suggests that experimental ischemic stroke induced by MCAO in young rat replicate long-term cognitive impairment and bihemispheric white matter degeneration observed in ischemic stroke patients. This model provides an invaluable tool for unraveling the mechanisms underlying post-stroke secondary white matter degeneration and its contribution to PSCID.

Keywords: Cognitive impairment; Ischemic stroke; MRI; Neuroinflammation; White matter hyperintensities; Whiter matter.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethical Approval: All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. Conflict of Interest: The authors declare no competing interests.

References

    1. Feigin VL, Norrving B, Mensah GA. Global burden of stroke. Circ Res. 2017;120(3):439–48. - PubMed - DOI
    1. McKevitt C, et al. Self-reported long-term needs after stroke. Stroke. 2011;42(5):1398–403. - PubMed - DOI
    1. Pollock A, et al. Top ten research priorities relating to life after stroke. Lancet Neurol. 2012;11(3):209. - PubMed - DOI
    1. Mijajlovic MD, et al. Post-stroke dementia - a comprehensive review. BMC Med. 2017;15(1):11. - PubMed - PMC - DOI
    1. Mok VC, et al. Early-onset and delayed-onset poststroke dementia - revisiting the mechanisms. Nat Rev Neurol. 2017;13(3):148–59. - PubMed - DOI

MeSH terms

LinkOut - more resources