Hanhan Liu1, Ari Dienel1, Karsten Schöller1, Susanne M Schwarzmaier1, Kathrin Nehrkorn1, Nikolaus Plesnila2, Nicole A Terpolilli1. 1. From the Institute for Stroke and Dementia Research (ISD) (H.L., S.M.S., K.N., N.P., N.A.T.), Department of Neurosurgery (A.D., K.S., N.A.T.), Walter-Brendel-Center for Experimental Medicine, Faculty of Medicine (A.D., N.A.T.), and Department of Anesthesiology (S.M.S.), University Hospital, LMU Munich, Germany; Department of Neurosurgery, University of Giessen, Germany (K.S.). 2. From the Institute for Stroke and Dementia Research (ISD) (H.L., S.M.S., K.N., N.P., N.A.T.), Department of Neurosurgery (A.D., K.S., N.A.T.), Walter-Brendel-Center for Experimental Medicine, Faculty of Medicine (A.D., N.A.T.), and Department of Anesthesiology (S.M.S.), University Hospital, LMU Munich, Germany; Department of Neurosurgery, University of Giessen, Germany (K.S.). nikolaus.plesnila@med.uni-muenchen.de.
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.
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.
Authors: Christian Fung; Werner J Z'Graggen; Stephan M Jakob; Jan Gralla; Matthias Haenggi; Hans-Ulrich Rothen; Pasquale Mordasini; Michael Lensch; Nicole Söll; Nicole Terpolilli; Sergej Feiler; Markus F Oertel; Andreas Raabe; Nikolaus Plesnila; Jukka Takala; Jürgen Beck Journal: Front Neurol Date: 2022-02-18 Impact factor: 4.003
Authors: Tobias P Schmidt; Walid Albanna; Miriam Weiss; Michael Veldeman; Catharina Conzen; Omid Nikoubashman; Christian Blume; Daniel S Kluger; Hans Clusmann; Sven H Loosen; Gerrit A Schubert Journal: Front Neurol Date: 2022-03-10 Impact factor: 4.003