Neutrophil elastase and neurovascular injury following focal stroke and reperfusion

Ann M. Stowe, Tracy L. Adair-Kirk, Ernesto R. Gonzales, Ronald S. Perez, Aarti R. Shah, Tae S. Park, Jeffrey M. Gidday

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Neutrophil elastase (NE) degrades basal lamina and extracellular matrix molecules, and recruits leukocytes during inflammation; however, a basic understanding of the role of NE in stroke pathology is lacking. We measured an increased number of extravascular NE-positive cells, as well as increased levels of tissue elastase protein and activity, following transient middle cerebral artery occlusion (tMCAo). Both pharmacologic inhibition of NE with ZN200355 (ZN), and genetic deletion of NE, significantly reduced infarct volume, blood-brain barrier disruption, vasogenic edema, and leukocyte-endothelial adherence 24 h after tMCAo. ZN also reduced infarct volume in MMP9-null mice following tMCAo. There were, however, no reductions in infarct volume or vasogenic edema in NE-null mice in two models of permanent middle cerebral artery occlusion. Our findings confirm the involvement of NE in neurovascular stroke pathology, when reperfusion allows neutrophils access to vulnerable brain, with pharmacologic or genetic inhibition of NE being both neuro- and vasculo-protective in this setting.

Original languageEnglish (US)
Pages (from-to)82-90
Number of pages9
JournalNeurobiology of Disease
Volume35
Issue number1
DOIs
StatePublished - Jul 1 2009

Keywords

  • Blood-brain barrier
  • Ischemia
  • Leukocyte-endothelial adherence
  • Protease
  • Transient middle cerebral artery occlusion
  • Vasogenic edema

ASJC Scopus subject areas

  • Neurology

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    Stowe, A. M., Adair-Kirk, T. L., Gonzales, E. R., Perez, R. S., Shah, A. R., Park, T. S., & Gidday, J. M. (2009). Neutrophil elastase and neurovascular injury following focal stroke and reperfusion. Neurobiology of Disease, 35(1), 82-90. https://doi.org/10.1016/j.nbd.2009.04.006