title: Nitric oxide inhalation reduces brain damage, prevents mortality, and improves neurological outcome after subarachnoid hemorrhage by resolving early pial microvasospasms.
abstract: Subarachnoid hemorrhage is a stroke subtype with particularly bad outcome. Recent findings suggest that constrictions of pial arterioles occurring early after hemorrhage may be responsible for cerebral ischemia and - subsequently - unfavorable outcome after subarachnoid hemorrhage. Since we recently hypothesized that the lack of nitric oxide may cause post-hemorrhagic microvasospasms, our aim was to investigate whether inhaled nitric oxide, a treatment paradigm selectively delivering nitric oxide to ischemic microvessels, is able to dilate post-hemorrhagic microvasospasms; thereby improving outcome after experimental subarachnoid hemorrhage. C57BL/6 mice were subjected to experimental SAH. Three hours after subarachnoid hemorrhage pial artery spasms were quantified by intravital microscopy, then mice received inhaled nitric oxide or vehicle. For induction of large artery spasms mice received an intracisternal injection of autologous blood. Inhaled nitric oxide significantly reduced number and severity of subarachnoid hemorrhage-induced post-hemorrhage microvasospasms while only having limited effect on large artery spasms. This resulted in less brain-edema-formation, less hippocampal neuronal loss, lack of mortality, and significantly improved neurological outcome after subarachnoid hemorrhage. This suggests that spasms of pial arterioles play a major role for the outcome after subarachnoid hemorrhage and that lack of nitric oxide is an important mechanism of post-hemorrhagic microvascular dysfunction. Reversing microvascular dysfunction by inhaled nitric oxide might be a promising treatment strategy for subarachnoid hemorrhage.
authors.affiliation: Department of Neurosurgery, University of Munich Medical Center, Munich, Germany.|Institute for Surgical Research, University of Munich Medical Center, Munich, Germany.|Institute for Stroke and Dementia Research, University of Munich Medical Center, Munich, Germany.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Terpolilli
authors.affiliation: Institute for Surgical Research, University of Munich Medical Center, Munich, Germany.
authors.forename: Sergej
authors.initials: S
authors.lastname: Feiler
authors.affiliation: Department of Neurosurgery, University of Munich Medical Center, Munich, Germany.|Institute for Surgical Research, University of Munich Medical Center, Munich, Germany.
authors.forename: Ari
authors.initials: A
authors.lastname: Dienel
authors.affiliation: Institute for Surgical Research, University of Munich Medical Center, Munich, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Müller
authors.affiliation: Department of Neurosurgery, University of Munich Medical Center, Munich, Germany.|Institute for Surgical Research, University of Munich Medical Center, Munich, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Heumos
authors.affiliation: Institute for Surgical Research, University of Munich Medical Center, Munich, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Friedrich
authors.affiliation: Department of Surgery, University of Zurich, Switzerland.
authors.forename: John
authors.initials: J
authors.lastname: Stover
authors.affiliation: Institute for Surgical Research, University of Munich Medical Center, Munich, Germany.
authors.forename: Serge
authors.initials: S
authors.lastname: Thal
authors.affiliation: Department of Neurosurgery, University of Munich Medical Center, Munich, Germany.|Institute for Surgical Research, University of Munich Medical Center, Munich, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Schöller
authors.affiliation: Institute for Surgical Research, University of Munich Medical Center, Munich, Germany nikolaus.plesnila@med.uni-muenchen.de.|Institute for Stroke and Dementia Research, University of Munich Medical Center, Munich, Germany.|Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Plesnila
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001929:Brain Edema / Q000517:prevention & control; D001930:Brain Injuries / Q000517:prevention & control; D006624:Hippocampus / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000187:drug effects* / Q000503:physiopathology; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016896:Treatment Outcome; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000517:prevention & control
chemical_list: D009569:Nitric Oxide
keywords: Cerebral perfusion; early brain injury; microvasospasm; nitric oxide; subarachnoid hemorrhage