The Role and Therapeutic Implications of Inflammation in the Pathogenesis of Brain Arteriovenous Malformations

Ashley R. Ricciardelli, Ariadna Robledo, Jason E. Fish, Peter T. Kan, Tajie H. Harris, Joshua D. Wythe

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

Brain arteriovenous malformations (bAVMs) are focal vascular lesions composed of abnormal vascular channels without an intervening capillary network. As a result, high-pressure arterial blood shunts directly into the venous outflow system. These high-flow, low-resistance shunts are composed of dilated, tortuous, and fragile vessels, which are prone to rupture. BAVMs are a leading cause of hemorrhagic stroke in children and young adults. Current treatments for bAVMs are limited to surgery, embolization, and radiosurgery, although even these options are not viable for ~20% of AVM patients due to excessive risk. Critically, inflammation has been suggested to contribute to lesion progression. Here we summarize the current literature discussing the role of the immune system in bAVM pathogenesis and lesion progression, as well as the potential for targeting inflammation to prevent bAVM rupture and intracranial hemorrhage. We conclude by proposing that a dysfunctional endothelium, which harbors the somatic mutations that have been shown to give rise to sporadic bAVMs, may drive disease development and progression by altering the immune status of the brain.

Original languageEnglish (US)
Article number2876
JournalBiomedicines
Volume11
Issue number11
DOIs
StatePublished - Nov 2023
Externally publishedYes

Keywords

  • blood brain barrier
  • brain arteriovenous malformation
  • cerebrovascular
  • endothelium
  • inflammation
  • microglia
  • neurovascular unit
  • vascular

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • General Biochemistry, Genetics and Molecular Biology

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