Stroke-prone salt-sensitive spontaneously hypertensive rats show higher susceptibility to spreading depolarization (SD) and altered hemodynamic responses to SD

Eun Jeung Kang, Ofer Prager, Svetlana Lublinsky, Ana I. Oliveira-Ferreira, Clemens Reiffurth, Sebastian Major, Dominik N. Müller, Alon Friedman, Jens P. Dreier

Research output: Contribution to journalArticlepeer-review

Abstract

Spreading depolarization (SD) occurs in a plethora of clinical conditions including migraine aura, delayed ischemia after subarachnoid hemorrhage and malignant hemispheric stroke. It describes waves of near-breakdown of ion homeostasis, particularly Na+ homeostasis in brain gray matter. SD induces tone alterations in resistance vessels, causing either hyperperfusion in healthy tissue; or hypoperfusion (inverse hemodynamic response = spreading ischemia) in tissue at risk. Observations from mice with genetic dysfunction of the ATP1A2-encoded α2-isoform of Na+/K+-ATPase (α2NaKA) suggest a mechanistic link between (1) SD, (2) vascular dysfunction, and (3) salt-sensitive hypertension via α2NaKA. Thus, α2NaKA-dysfunctional mice are more susceptible to SD and show a shift toward more inverse hemodynamic responses. α2NaKA-dysfunctional patients suffer from familial hemiplegic migraine type 2, a Mendelian model disease of SD. α2NaKA-dysfunctional mice are also a genetic model of salt-sensitive hypertension. To determine whether SD thresholds and hemodynamic responses are also altered in other genetic models of salt-sensitive hypertension, we examined these variables in stroke-prone spontaneously hypertensive rats (SHRsp). Compared with Wistar Kyoto control rats, we found in SHRsp that electrical SD threshold was significantly reduced, propagation speed was increased, and inverse hemodynamic responses were prolonged. These results may have relevance to both migraine with aura and stroke.

Original languageAmerican English
Pages (from-to)210-230
Number of pages21
JournalJournal of Cerebral Blood Flow and Metabolism
Volume43
Issue number2
DOIs
StatePublished - 1 Feb 2023

Keywords

  • Spreading depolarization
  • hypertension
  • migraine
  • salt-sensitivity
  • spreading depression
  • stroke

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Neurology
  • Cardiology and Cardiovascular Medicine

Fingerprint

Dive into the research topics of 'Stroke-prone salt-sensitive spontaneously hypertensive rats show higher susceptibility to spreading depolarization (SD) and altered hemodynamic responses to SD'. Together they form a unique fingerprint.

Cite this