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| Item Type: | Article |
|---|---|
| Title: | Stroke-prone salt-sensitive spontaneously hypertensive rats show higher susceptibility to spreading depolarization (SD) and altered hemodynamic responses to SD |
| Creators Name: | Kang, E.J., Prager, O., Lublinsky, S., Oliveira-Ferreira, A.I., Reiffurth, C., Major, S., Mueller, D.N., Friedman, A. and Dreier, J.P. |
| 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 α(2)-isoform of Na(+)/K(+)-ATPase (α(2)NaKA) suggest a mechanistic link between (1) SD, (2) vascular dysfunction, and (3) salt-sensitive hypertension via α(2)NaKA. Thus, α(2)NaKA-dysfunctional mice are more susceptible to SD and show a shift toward more inverse hemodynamic responses. α(2)NaKA-dysfunctional patients suffer from familial hemiplegic migraine type 2, a Mendelian model disease of SD. α(2)NaKA-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. |
| Keywords: | Spreading Depolarization, Spreading Depression, Salt-Sensitivity, Hypertension, Stroke, Migraine, Animals, Mice, Rats |
| Source: | Journal of Cerebral Blood Flow and Metabolism |
| ISSN: | 0271-678X |
| Publisher: | Sage Publications |
| Volume: | 43 |
| Number: | 2 |
| Page Range: | 210-230 |
| Date: | February 2023 |
| Official Publication: | https://doi.org/10.1177/0271678x221135085 |
| PubMed: | View item in PubMed |
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