Monitoring stroke progression: In vivo imaging of cortical perfusion, blood-brain barrier permeability and cellular damage in the rat photothrombosis model

Karl Schoknecht, Ofer Prager, Udi Vazana, Lyn Kamintsky, Denise Harhausen, Marietta Zille, Lena Figge, Yoash Chassidim, Eyk Schellenberger, Richard Kovács, Uwe Heinemann, Alon Friedman

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Focal cerebral ischemia is among the main causes of death and disability worldwide. The ischemic core often progresses, invading the peri-ischemic brain; however, assessing the propensity of the peri-ischemic brain to undergo secondary damage, understanding the underlying mechanisms, and adjusting treatment accordingly remain clinically unmet challenges. A significant hallmark of the peri-ischemic brain is dysfunction of the blood-brain barrier (BBB), yet the role of disturbed vascular permeability in stroke progression is unclear. Here we describe a longitudinal in vivo fluorescence imaging approach for the evaluation of cortical perfusion, BBB dysfunction, free radical formation and cellular injury using the photothrombosis vascular occlusion model in male Sprague Dawley rats. Blood-brain barrier dysfunction propagated within the peri-ischemic brain in the first hours after photothrombosis and was associated with free radical formation and cellular injury. Inhibiting free radical signaling significantly reduced progressive cellular damage after photothrombosis, with no significant effect on blood flow and BBB permeability. Our approach allows a dynamic follow-up of cellular events and their response to therapeutics in the acutely injured cerebral cortex.

Original languageEnglish
Pages (from-to)1791-1801
Number of pages11
JournalJournal of Cerebral Blood Flow and Metabolism
Volume34
Issue number11
DOIs
StatePublished - 1 Jan 2014

Keywords

  • blood-brain barrier
  • brain imaging
  • cell death mechanisms
  • cerebral blood flow
  • focal ischemia

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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