title: Aneurysmal Subarachnoid Hemorrhage and Neuroinflammation: A Comprehensive Review.
abstract: Aneurysmal subarachnoid hemorrhage (SAH) can lead to devastating outcomes including vasospasm, cognitive decline, and even death. Currently, treatment options are limited for this potentially life threatening injury. Recent evidence suggests that neuroinflammation plays a critical role in injury expansion and brain damage. Red blood cell breakdown products can lead to the release of inflammatory cytokines that trigger vasospasm and tissue injury. Preclinical models have been used successfully to improve understanding about neuroinflammation following aneurysmal rupture. The focus of this review is to provide an overview of how neuroinflammation relates to secondary outcomes such as vasospasm after aneurysmal rupture and to critically discuss pharmaceutical agents that warrant further investigation for the treatment of subarachnoid hemorrhage. We provide a concise overview of the neuroinflammatory pathways that are upregulated following aneurysmal rupture and how these pathways correlate to long-term outcomes. Treatment of aneurysm rupture is limited and few pharmaceutical drugs are available. Through improved understanding of biochemical mechanisms of injury, novel treatment solutions are being developed that target neuroinflammation. In the final sections of this review, we highlight a few of these novel treatment approaches and emphasize why targeting neuroinflammation following aneurysmal subarachnoid hemorrhage may improve patient care. We encourage ongoing research into the pathophysiology of aneurysmal subarachnoid hemorrhage, especially in regards to neuroinflammatory cascades and the translation to randomized clinical trials.
authors.affiliation: Department of Neurosurgery, West Virginia University School of Medicine, Morgantown, WV 26505, USA. Bwold@mix.wvu.edu.
authors.forename: Brandon P
authors.initials: BP
authors.lastname: Lucke-Wold
authors.affiliation: Department of Basic Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown, WV 26505, USA. logsdoa@gmail.com.
authors.forename: Aric F
authors.initials: AF
authors.lastname: Logsdon
authors.affiliation: McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, Hamilton, ON L8S 4K1, Canada. branavan.manoranjan@medportal.ca.
authors.forename: Branavan
authors.initials: B
authors.lastname: Manoranjan
authors.affiliation: Department of Neurosurgery, West Virginia University School of Medicine, Morgantown, WV 26505, USA. rcturner@hsc.wvu.edu.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Turner
authors.affiliation: Department of Neurobiology and Anatomy, University of Rochester Medical Center, Rochester, NY 14642, USA. evan_mcconnell@urmc.rochester.edu.
authors.forename: Evan
authors.initials: E
authors.lastname: McConnell
authors.affiliation: Department of Neurobiology and Anatomy, University of Rochester Medical Center, Rochester, NY 14642, USA. edward_vates@urmc.rochester.edu.
authors.forename: George Edward
authors.initials: GE
authors.lastname: Vates
authors.affiliation: Department of Basic Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown, WV 26505, USA. jdhuber@hsc.wvu.edu.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Huber
authors.affiliation: Department of Neurosurgery, West Virginia University School of Medicine, Morgantown, WV 26505, USA. crosen@hsc.wvu.edu.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Rosen
authors.affiliation: Departments of Neurosurgery, Pathology, and Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. msimard@smail.umaryland.edu.
authors.forename: J Marc
authors.initials: JM
authors.lastname: Simard
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000276:immunology / Q000473:pathology*; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000276:immunology / Q000473:pathology; D010447:Peptide Hydrolases / Q000032:analysis / Q000276:immunology; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D014661:Vasoconstriction
chemical_list: D016207:Cytokines; D010447:Peptide Hydrolases
keywords: aneurysmal subarachnoid hemorrhage; cerebral vasospasm; neuroinflammation; novel treatments