Chronic hypertension and perfusion deficits conjointly affect disease outcome after tPA treatment in a rodent model of thromboembolic stroke

Bart A.A. Franx*, Ivo A.C.W. Tiebosch, Annette van der Toorn, Rick M. Dijkhuizen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Futile recanalization hampers prognoses for ischemic stroke patients despite successful recanalization therapy. Allegedly, hypertension and reperfusion deficits contribute, but a better understanding is needed of how they interact and mediate disease outcome. We reassessed data from spontaneously hypertensive and normotensive Wistar-Kyoto rats (male, n = 6–7/group) that were subjected to two-hour embolic middle cerebral artery occlusion and thrombolysis in preclinical trials. Serial MRI allowed lesion monitoring and parcellation of regions-of-interest that represented infarcted (core) or recovered (perilesional) tissue. Imaging markers of hemodynamics and blood-brain barrier (BBB) status were related to tissue fate and neurological outcome. Despite comparable ischemic severity during occlusion between groups, hypertensive rats temporarily developed larger lesions after recanalization, with permanently aggravated vasogenic edema and BBB permeability. One day post-stroke, cerebral blood flow (CBF) was variably restored, but blood transit times were consistently prolonged in hypertensives. Compared to the core, perilesional CBF was normo-to-hyperperfused in both groups, yet this pattern reversed after seven days. Volumes of hypo- and hyperperfusion developed irrespective of strain, differentially associating with final infarct volume and behavioral outcome. Incomplete reperfusion and cerebral injury after thrombolysis were augmented in hypertensive rats. One day after thrombolysis, fractional volumes of hypoperfusion associated with worsened outcomes, while fractional volumes of hyperperfusion appeared beneficial or benign.

Original languageEnglish
Pages (from-to)831-841
Number of pages11
JournalJournal of Cerebral Blood Flow and Metabolism
Volume45
Issue number5
Early online date22 Jan 2025
DOIs
Publication statusPublished - May 2025

Keywords

  • cerebral hemodynamics
  • Embolic stroke
  • hypertension
  • magnetic resonance imaging
  • thrombolysis

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