Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 26 декабря 2018 г.
Аннотация:Background and Purpose—Subarachnoid hemorrhage (SAH) is a complex stroke subtype characterized by an initial brain
injury, followed by delayed cerebrovascular constriction and ischemia. Current therapeutic strategies nonselectively
curtail exacerbated cerebrovascular constriction, which necessarily disrupts the essential and protective process of
cerebral blood flow autoregulation. This study identifies a smooth muscle cell autocrine/paracrine signaling network that
augments myogenic tone in a murine model of experimental SAH: it links tumor necrosis factor-α (TNFα), the cystic
fibrosis transmembrane conductance regulator, and sphingosine-1-phosphate signaling.
Methods—Mouse olfactory cerebral resistance arteries were isolated, cannulated, and pressurized for in vitro vascular
reactivity assessments. Cerebral blood flow was measured by speckle flowmetry and magnetic resonance imaging.
Standard Western blot, immunohistochemical techniques, and neurobehavioral assessments were also used.
Results—We demonstrate that targeting TNFα and sphingosine-1-phosphate signaling in vivo has potential therapeutic
application in SAH. Both interventions (1) eliminate the SAH-induced myogenic tone enhancement, but otherwise
leave vascular reactivity intact; (2) ameliorate SAH-induced neuronal degeneration and apoptosis; and (3) improve
neurobehavioral performance in mice with SAH. Furthermore, TNFα sequestration with etanercept normalizes cerebral
perfusion in SAH.
Conclusions—Vascular smooth muscle cell TNFα and sphingosine-1-phosphate signaling significantly enhance cerebral
artery tone in SAH; anti-TNFα and anti–sphingosine-1-phosphate treatment may significantly improve clinical
outcome.