title: Pathological mechanisms underlying aneurysmal subarachnoid haemorrhage and vasospasm.
abstract: Aneurysmal subarachnoid haemorrhage is a cerebrovascular disease associated with an overall mortality as high as 50%. Delayed ischaemic neurologic deficits are a major contributor to this statistic, as well as the significant morbidity associated with the disease. Studies examining the pathophysiologic events causing these devastating changes in cerebral blood flow have identified several mechanisms which are thought to contribute to the development of delayed ischaemic neurological deficits, perhaps the most damaging of which are increased intracranial pressure and cerebral vasospasm. In addition, the presence of blood in the subarachnoid space can trigger a myriad of reactions resulting in increased capillary permeability, breakdown of the blood-brain barrier, and inflammation in surrounding neural tissue that adds to the devastating effects of haemorrhage. A detailed understanding of the post-haemorrhagic cellular and molecular changes that contribute to the development of cerebral ischaemia and vasospasm is imperative to the formulation of treatment and prevention options for subarachnoid haemorrhage patients. Despite a large body of research within this field, a complete understanding of rupture and vasospasm remains elusive. This study reviews the role of vasoactive substances, such as endothelin-1, as well as the histochemistry and molecular pathology of post-haemorrhage inflammation in the development of vasospasm and cerebral ischaemia.
authors.affiliation: Department of Neurological Surgery, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, AB-136, Boston, MA 02115, USA. Electronic address: DLP628@gmail.com.
authors.forename: David L
authors.initials: DL
authors.lastname: Penn
authors.affiliation: Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Samantha R
authors.initials: SR
authors.lastname: Witte
authors.affiliation: Department of Neurological Surgery, University of Miami, Miami, FL, USA.
authors.forename: Ricardo J
authors.initials: RJ
authors.lastname: Komotar
authors.affiliation: Department of Neurological Surgery, New York-Presbyterian Hospital, Columbia University, New York, NY, USA.
authors.forename: E
authors.initials: E
authors.lastname: Sander Connolly
mesh_terms: D006801:Humans; D002532:Intracranial Aneurysm / Q000150:complications*; D013345:Subarachnoid Hemorrhage / Q000209:etiology / Q000276:immunology / Q000473:pathology; D020301:Vasospasm, Intracranial / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism
keywords: Aneurysms; Endothelin; Matrix metalloproteinases; Subarachnoid haemorrhage; Vasospasm