Microvasospasms After Experimental Subarachnoid Hemorrhage Do Not Depend on Endothelin A Receptors

Liu, Hanhan; Dienel, Ari; Schöller, Karsten; Schwarzmaier, Susanne M.; Nehrkorn, Kathrin; Plesnila, Nikolaus and Terpolilli, Nicole A. (2018): Microvasospasms After Experimental Subarachnoid Hemorrhage Do Not Depend on Endothelin A Receptors. In: Stroke, Vol. 49, No. 3: pp. 693-699

Abstract

Background and Purpose-Perturbations in cerebral microcirculation (eg, microvasospasms) and reduced neurovascular communication determine outcome after subarachnoid hemorrhage (SAH). ET-1 (endothelin-1) and its receptors have been implicated in the pathophysiology of large artery spasms after SAH;however, their role in the development of microvascular dysfunction is currently unknown. Here, we investigated whether inhibiting ETA (endothelin A) receptors can reduce microvasospasms after experimentally induced SAH. Methods-SAH was induced in male C57BL/6 mice by filament perforation of the middle cerebral artery. Three hours after SAH, a cranial window was prepared and the pial and parenchymal cerebral microcirculation was measured in vivo using two-photon microscopy before, during, and after administration of the ETA receptor inhibitor clazosentan. In separate experiments, the effect of clazosentan treatment on neurological outcome was measured 3 days after SAH. Results: Clazosentan treatment had no effect on the number or severity of SAH-induced cerebral microvasospasms nor did it affect neurological outcome. Conclusions: Our results indicate that ETA receptors, which mediate large artery spasms after SAH, do not seem to play a role in the development of microarterial spasms, suggesting that posthemorrhagic spasms are mediated by distinct mechanisms in large and small cerebral vessels. Given that cerebral microvessel dysfunction is a key factor for outcome after SAH, further research into the mechanisms that underlie posthemorrhagic microvasospasms is urgently needed.

• Item Type: Journal article
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 0039-2499
• Alliance/National Licence: This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
• Language: English