A role of the sodium pump in spreading ischemia in rats.
J Cereb Blood Flow Metab
; 37(5): 1687-1705, 2017 May.
Article
en En
| MEDLINE
| ID: mdl-26994042
ABSTRACT
In rats, spreading depolarization induces vasodilation/hyperemia in naïve tissue but the inverse response when artificial cerebrospinal fluid is topically applied to the brain containing (a) a nitric oxide-lowering agent and (b) elevated K+. The inverse response is characterized by severe vasoconstriction/ischemia. The perfusion deficit runs together with the depolarization in the tissue (=spreading ischemia). Here, we found in male Wistar rats that pre-treatment with artificial cerebrospinal fluid containing elevated K+ in vivo led to a selective decline in α2/α3 Na+/K+-ATPase activity, determined spectrophotometrically ex vivo. Moreover, spreading ischemia, recorded with laser-Doppler flowmetry and electrocorticography, resulted from artificial cerebrospinal fluid containing a nitric oxide-lowering agent in combination with the Na+/K+-ATPase inhibitor ouabain at a concentration selectively inhibiting α2/α3 activity. Decline in α2/α3 activity results in increased Ca2+ uptake by internal stores of astrocytes, vascular myocytes, and pericytes since Ca2+ outflux via plasmalemmal Na+/Ca2+-exchanger declines. Augmented Ca2+ mobilization from internal stores during spreading depolarization might enhance vasoconstriction, thus, contributing to spreading ischemia. Accordingly, spreading ischemia was significantly shortened when intracellular Ca2+ stores were emptied by pre-treatment with thapsigargin, an inhibitor of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA). These findings might have relevance for clinical conditions, in which spreading ischemia occurs such as delayed cerebral ischemia after subarachnoid hemorrhage.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Depresión de Propagación Cortical
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Vasoconstricción
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Isquemia Encefálica
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Circulación Cerebrovascular
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ATPasa Intercambiadora de Sodio-Potasio
Límite:
Animals
Idioma:
En
Revista:
J Cereb Blood Flow Metab
Año:
2017
Tipo del documento:
Article
País de afiliación:
Alemania