TY - JOUR
T1 - Chronic hypertension and perfusion deficits conjointly affect disease outcome after tPA treatment in a rodent model of thromboembolic stroke
AU - Franx, Bart A.A.
AU - Tiebosch, Ivo A.C.W.
AU - van der Toorn, Annette
AU - Dijkhuizen, Rick M.
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/5
Y1 - 2025/5
N2 - 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.
AB - 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.
KW - cerebral hemodynamics
KW - Embolic stroke
KW - hypertension
KW - magnetic resonance imaging
KW - thrombolysis
UR - http://www.scopus.com/inward/record.url?scp=85216181019&partnerID=8YFLogxK
U2 - 10.1177/0271678X241310732
DO - 10.1177/0271678X241310732
M3 - Article
C2 - 39843421
AN - SCOPUS:85216181019
SN - 0271-678X
VL - 45
SP - 831
EP - 841
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
IS - 5
ER -