The Neurovascular Unit as a Locus of Injury in Low-Level Blast-Induced Neurotrauma

Gregory A. Elder, Miguel A. Gama Sosa, Rita De Gasperi, Georgina Perez Garcia, Gissel M. Perez, Rania Abutarboush, Usmah Kawoos, Carolyn W. Zhu, William G.M. Janssen, James R. Stone, Patrick R. Hof, David G. Cook, Stephen T. Ahlers

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

Blast-induced neurotrauma has received much attention over the past decade. Vascular injury occurs early following blast exposure. Indeed, in animal models that approximate human mild traumatic brain injury or subclinical blast exposure, vascular pathology can occur in the presence of a normal neuropil, suggesting that the vasculature is particularly vulnerable. Brain endothelial cells and their supporting glial and neuronal elements constitute a neurovascular unit (NVU). Blast injury disrupts gliovascular and neurovascular connections in addition to damaging endothelial cells, basal laminae, smooth muscle cells, and pericytes as well as causing extracellular matrix reorganization. Perivascular pathology becomes associated with phospho-tau accumulation and chronic perivascular inflammation. Disruption of the NVU should impact activity-dependent regulation of cerebral blood flow, blood–brain barrier permeability, and glymphatic flow. Here, we review work in an animal model of low-level blast injury that we have been studying for over a decade. We review work supporting the NVU as a locus of low-level blast injury. We integrate our findings with those from other laboratories studying similar models that collectively suggest that damage to astrocytes and other perivascular cells as well as chronic immune activation play a role in the persistent neurobehavioral changes that follow blast injury.

Original languageEnglish
Article number1150
JournalInternational Journal of Molecular Sciences
Volume25
Issue number2
DOIs
StatePublished - Jan 2024

Keywords

  • animal models
  • astrocytes
  • blast
  • inflammation
  • traumatic brain injury
  • vascular pathology

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