Preserving Blood-Brain Barrier Integrity in Ischemic Stroke: a Review on MSCs-sEVs Content and Potential Molecular Targets

Mol Neurobiol. 2025 Aug;62(8):10981-11007. doi: 10.1007/s12035-025-04956-9. Epub 2025 Apr 21.

Abstract

Ischemic stroke (IS) is a life-threatening condition that constitutes the second leading cause of death globally. Despite its high impact on public health, there is a shortage of treatments due to the complexity of the cellular and molecular mechanisms implicated. One main limiting factor for successful IS therapeutic intervention is stroke-induced blood-brain barrier (BBB) damage, particularly over tight junction proteins (TJs). BBB disruption is a well-established feature of IS, accelerating ischemic tissue damage and worsening prognosis. In recent years, mesenchymal stem cells (MSCs) and their small extracellular vesicles (MSCs-sEVs) have emerged as promising therapeutic interventions for several neurological disorders, including IS. However, its effects on BBB repair after IS are not completely understood. In this review, we will discuss novel experimental evidence of MSCs-sEVs effects in BBB protection and highlight the relevance of molecules reported in MSCs-sEVs, their potential cellular and molecular targets, and putative mechanisms implicated in BBB repair, providing a promising research avenue that may translate into effective therapeutic strategies for IS.

Keywords: Blood–brain barrier; Exosomes; Extracellular vesicles; Ischemic stroke; Mesenchymal stem cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Blood-Brain Barrier* / metabolism
  • Blood-Brain Barrier* / pathology
  • Extracellular Vesicles* / metabolism
  • Humans
  • Ischemic Stroke* / metabolism
  • Ischemic Stroke* / pathology
  • Ischemic Stroke* / therapy
  • Mesenchymal Stem Cells* / metabolism