A versatile murine model of subcortical white matter stroke for the study of axonal degeneration and white matter neurobiology

Stefanie Nunez, M. Mehdi Doroudchi, Amy J. Gleichman, Kwan Ng, Irene L. Llorente, Elif G. Sozmen, S. Thomas Carmichael, Jason D. Hinman

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Stroke affecting white matter accounts for up to 25% of clinical stroke presentations, occurs silently at rates that may be 5-10 fold greater, and contributes significantly to the development of vascular dementia. Few models of focal white matter stroke exist and this lack of appropriate models has hampered understanding of the neurobiologic mechanisms involved in injury response and repair after this type of stroke. The main limitation of other subcortical stroke models is that they do not focally restrict the infarct to the white matter or have primarily been validated in non-murine species. This limits the ability to apply the wide variety of murine research tools to study the neurobiology of white matter stroke. Here we present a methodology for the reliable production of a focal stroke in murine white matter using a local injection of an irreversible eNOS inhibitor. We also present several variations on the general protocol including two unique stereotactic variations, retrograde neuronal tracing, as well as fresh tissue labeling and dissection that greatly expand the potential applications of this technique. These variations allow for multiple approaches to analyze the neurobiologic effects of this common and understudied form of stroke.

Original languageEnglish (US)
Article numbere53404
JournalJournal of Visualized Experiments
Issue number109
StatePublished - Mar 17 2016
Externally publishedYes


  • Axonal degeneration
  • Issue 109
  • Lacunar infarct
  • Medicine
  • Neuroscience
  • Stroke modeling
  • White matter stroke

ASJC Scopus subject areas

  • Neuroscience(all)
  • Chemical Engineering(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


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